Advertise on podcast: The Stem Cell Report with Janet Rossant

Epigenetic regulation of gene expression is an important mechanism in development and disease. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications for RNA and has been shown to play critical roles in processes such as embryo development, cancer, and stress responses. Our guests today investigate how m6A regulates X chromosome dosage compensation to ensure proper balance of gene expression from X chromosomes between sexes. X-chromosome dosage compensation is accomplished through two complementary mechanisms. First, X-chromosome inactivation (XCI) silences one of the two X chromosomes in female cells. Second, the remaining active X chromosome is transcriptionally upregulated so that its gene expression levels are balanced with those of the autosomes, a process known as X-to-autosome (X-to-A) compensation. The authors dissect the distinct contributions of m6A RNA methylation to XCI versus X-to-A compensation across multiple embryonic lineages, providing deeper insights into the epigenetic regulation of early development. Guests Srimonta Gayen, PhD, Department of Developmental Biology and Genetics, Indian Institute of Science, India Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content Paper link: "The role of m6A RNA methylation in the maintenance of X chromosome inactivation and X-to-autosome dosage compensation in early embryonic lineages," Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR Across more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to advancing stem cell research and its translation to medicine. ISSCR Staff Keith Alm, Chief Executive Officer Shuangshuang Du, Scientific Programs Manager Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Director Hunter Reed, Senior Marketing Coordinator

The human intestinal epithelial barrier comprises diverse proliferative, secretory and absorptive cell types that facilitate nutrient digestion and absorption and protect against harmful environmental agents. The barrier and its function can vary between individuals due to genetic differences thus impact processes such as digestion, drug metabolism, and drug sensitivity. Our guests today investigated the effect of diverse culture conditions on the cell type composition, gene expression profiles, and maturation status of human pluripotent stem cell-derived intestinal epithelial cells in three different model systems. Their research provides insight into the relevant conditions and systems for modeling specific intestinal functions and highlights the importance of personalized intestinal model systems.  Guests Sebo Withoff is an Associate Professor in the Department of Genetics at the University of Groningen in the Netherlands.  Iris Jonkers is an Adjunct Professor and Rosalind Franklin Fellow in the Department of Genetics at University of Groningen in the Netherlands.  Renée Moerkens is a Postdoctoral Fellow at Ombion in the Netherlands.  Joram Mooiweer is a PhD Student in the Department of Genetics at the University of Groningen, in the Netherlands.  Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Director Hunter Reed, Senior Marketing Coordinator

The blood-brain barrier (BBB), formed by brain endothelial cells, pericytes, and astrocytes, is organized into a neurovascular unit that regulates the exchange of proteins between blood circulation and brain parenchyma. Human stem-cell-based models using brain endothelial cells are a powerful tool to investigate how disease-related conditions might affect the blood-brain barrier integrity. However, the cell type composition is critical to faithfully model transcytosis across the blood-brain barrier. Our guests today developed a blood-brain model using induced pluripotent stem cells (iPSCs)-derived endothelial cells with brain-specific identity. Using this model they were able to investigate how disease risk factors affect intracellular transport and reveal a new role for ApoE4 in the regulation of iron metabolism at the blood-brain barrier.  Guests Roberto Villaseñor, Principal Scientist and Laboratory Head of the Brain Delivery, Neuroscience and Rare Diseases at the Roche Innovation Center in Basel, Switzerland  Martina Pigoni, Senior Discovery Scientist at Roche Innovation Center in Basel, Switzerland  Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Director Hunter Reed, Senior Marketing Coordinator

Hematopoietic stem cells (HSCs) normally reside in the bone marrow niche but can traffic across the bone marrow endothelium into the bloodstream to populate different niches. This process of HSC mobilization from the bone marrow to the blood, is an increasingly favored procedure to obtain HSCs for hematopoietic cell transplantation therapy. Though mobilization is robust in many donors due to years of refined protocols and drug combinations, the process remains difficult or contraindicated among substantial patient subgroups. Using the current standard of care, up to 30% of patients fail to mobilize HSCs and some patients cannot tolerate the current mobilization procedures. Today’s guests will discuss their research using vascular endothelial growth factor, known as VEGF, as an alternative method of mobilization, the mechanisms underlying it, and the implications for improving patient outcomes. Guests Stephanie Smith-Berdan, MS, Institute for the Biology of Stem Cells, Department of Biomolecular, Engineering, University of California, Santa Cruz, USA.  Camilla Forsberg, PhD, Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, USA.  Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content Paper link: Vascular endothelial growth factor-induced vascular permeability results in drastic and reversible hematopoietic stem cell mobilization, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Director Hunter Reed, Senior Marketing Coordinator

The role of neuronal influences on cancer pathogenesis and progression is increasingly appreciated in the nervous system. Neurons have been shown to enhance the proliferation and migration of gliomas, a glial-derived tumor of the CNS, via diffusible paracrine factors or synaptic inputs onto tumor cells. In glioblastomas, a highly aggressive glioma, mostly glutamatergic inputs have been identified. While the potential for glioblastomas to receive projections from neurons of other neurotransmitter subtypes, such as from cholinergic neurons, has recently been discovered in xenotransplantation models, whether synapses can form between human cholinergic neurons and glioblastoma cells and consequences of these inputs and other non-synaptic mechanisms are still unknown.    Human induced pluripotent stem cell-based models have been emerging as a powerful platform for studying human-specific disease mechanisms. Today’s guests developed a co-culture model for the study of neuron-tumor interactions by combining patient derived glioblastoma organoids and hiPSC-derived cholinergic neurons. They will discuss their recent findings and what it means for understanding and potentially treating a tumor for which there is no known cure.  Guests Guo-li Ming, MD, PhD, Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania Hongjun Song, PhD, Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania Yusha Sun, Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content Paper link:  Cholinergic neuron-to-glioblastoma synapses in a human iPSC-derived co-culture model, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Director Hunter Reed, Senior Marketing Coordinator

Skeletal muscle is one of the most abundant tissues in the human body, representing approximately 40% of body weight. Under certain circumstances, skeletal muscle can be regenerated through satellite cells, a reservoir of quiescent muscle stem cells, that can be activated with injury or in certain diseases and give rise to newly formed multi-nucleated myotubes and myofibers. However, the regenerative potential of muscle is diminished or is completely absent in the course of normal aging, certain diseases, and space travel. For example, time spent in microgravity can have a profound impact on human physiology, especially the muscular system, as astronauts lose up to 20% of their lean muscle mass and up to half of their strength.   The identification of countermeasures against the effects of muscle regeneration, including microgravity, is an increasing priority for an aging population and continued space travel. Experiments in microgravity, conducted on the International Space Station, offer a unique opportunity to understand muscle regeneration and the effects of microgravity. Our guests today will discuss muscle regeneration, their muscle-on-a-chip platform that mimics salient aspects of impaired muscle regeneration, and the feasibility of drug screening in microgravity. Guests Ngan Huang, PhD, Department of Cardiothoracic Surgery, Stanford University, USA Soochi Kim, PhD, Department of Biotechnology and Bioinformatics, Korea University, Korea Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content Paper link:  Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Director Hunter Reed, Senior Marketing Coordinator

The potential of pluripotent stem cells and the ability to scale and differentiate them to generate large numbers of enriched cell populations has created new opportunities and approaches to treat human disease. Preclinical proof-of-principle data demonstrates that stem cell-derived neural grafts can be used to reverse symptoms of multiple neurological conditions, including Parkinson’s Disease. Cell grafts enriched with dopaminergic neurons, can structurally and functionally integrate in the brain of Parkinson’s Disease models to reverse motor deficits, a finding which has launched several clinical trials. While the results in animal models is essential proof-of-concept, the survival and integration of these cells is suboptimal compared to treatments from fetal-derived ventral midbrain grafts.  An area of preclinical and clinical research showing promise in influencing neuronal survival and plasticity is exercise. The benefits of exercise on neural function and disease progression have been widely reported and they have also been shown to enhance the survival and integration of transplanted cells in models of some neurological diseases. However, there is limited data on the benefit of exercise on the functional outcomes of neural grafts in Parkinson’s Disease models. The guests on today’s program will discuss their recent study looking at the effect of exercise on cellular engraftment and functional recovery in animal models of Parkinson’s Disease and the implications for clinical outcomes.  Guests Clare Parish, PhD, The Florey Institute of Neuroscience and Mental Health and University of Melbourne, Australia Niamh Moriarty, PhD, The Florey Institute of Neuroscience and Mental Health and University of Melbourne, Australia Supporting Content Paper link: Exercise promotes the functional integration of human stem cell-derived neural grafts in a rodent model of Parkinson’s disease Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Advisor Hunter Reed, Senior Marketing Coordinator

Parent-specific epigenetic marks (imprints) leading to parent-specific gene expression are crucial for normal growth and development, yet their mechanisms of establishment and maintenance are not fully understood. In humans, approximately 200 imprinted genes have been discovered, and improper imprinting can manifest in growth restriction, obesity, intellectual disabilities, behavioral abnormalities, and an increased risk of certain cancers. While the use of pluripotent stem cells, especially those in the naïve state, have advanced aspects of modeling early development, a persistent issue hampering bona fide naïve hPSCs is the erosion of imprints. Our guests on today's episode will discuss genomic imprinting, its function, impact, and a new reporter system of imprinted gene expression in hPSCs that enables real-time visualization of loss-of-imprinting at single-cell resolution. This assay provides an important tool to help discover how to improve the imprint fidelity of naïve hPSCs and hence their application for studies of human development and regeneration. Guests Thorold Theunissen, PhD, Department of Developmental Biology, Washington University in St Louis, USA Gal Keshet, The Azrieli Center for Stem Cells and Genetic Research, The Hebrew University of Jerusalem, Israel Supporting Content Tracking and mitigating imprint erasure during induction of naïve human pluripotency at single-cell resolution Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Senior Marketing Manager Jack Mosher, Scientific Advisor Hunter Reed, Senior Marketing Coordinator Voice Work Ben Snitkoff

The mature lung in both humans and mice is highly vascularized, with approximately 30% of all cells being endothelial cells (ECs). The blood vessels have a physiological role in gas exchange within the tissue, but the vascular cells have additional role(s) beyond supplying oxygen and nutrients to the tissue.  For example, the adult lung endothelium responds to injury by activating pathways for alveolar re epithelialization and during embryonic development, disrupting vascularization ex vivo affects the stereotypical pattern of airway branching, consistent with a perfusion-independent crosstalk between the endothelium and epithelium. Today’s guests explore the molecular contribution of ECs and pericytes to the differentiation of distal airway progenitor cells into mature alveolar epithelial cells and will discuss the broader role of the vascular system in the maturation and regeneration or the lung.  Guests Paolo Panza is with the Justus-Liebig University Giessen, Germany. He previously was a postdoctoral fellow in Didier Stainier’s laboratory at the Max Planck Institute for Heart and Lung Research and received his PhD from University of Tübingen, Germany. Professor Panza is the first author of the recently published paper, The lung microvasculature promotes alveolar types 2 cell differentiation via secreted SPARCL1, which forms the basis of our discussion today.  Mingxia Gu is an Associate Professor at the David Geffen School of Medicine at the University of California, Los Angeles. She received her PhD from a joint training program between Peking University, Beijing, China and Stanford University, USA, and was a postdoctoral fellow in Marlene Rabinovitch’s laboratory at Stanford. The Gu laboratory studies the regeneration lung, and vasculature among other tissues. Professor Gu is an elected Fellow of the American Heart Association and a member of Early Career Editorial Board for Stem Cell Reports. Host Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation Supporting Content The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Marketing Manager Jack Mosher, Scientific Advisor Hunter Reed, Senior Marketing Coordinator Voice Work Ben Snitkoff

In this special edition of the podcast, we will talk with the new Editor-in-Chief Janet Rossant and hear about her vision for the journal, its promising future, and what she sees as some of the exciting prospects over the horizon for stem cell research. We will also talk with Yvonne Fisher, the journal’s Managing Editor, and Jack Mosher of the ISSCR, about the evolution of the journal and its role in the Society. Guests Janet Rossant is the new Editor-in-Chief of Stem Cell Reports. She holds an appointment as the Chief of Research Emeritus and Senior Scientist at The Hospital for Sick Children and is the President and Scientific Director of the Gairdner Foundation. Widely recognized as an expert in embryonic development, Professor Rossant has been recognized for her contributions to science with awards, including the Ross G. Harrison Medal (lifetime achievement award) from the International Society of Developmental Biologists, the March of Dimes Prize in Developmental Biology, the Conklin Medal from the Society for Developmental Biology, and the 2018 L’Oréal For Women in Science Award. She is a Fellow of the Royal Societies of both London and Canada, and an International member of the US National Academy of Sciences. She previously served as President of the ISSCR. Learn more about Stem Cell Reports editorial team. Yvonne Fisher is the Managing Editor of Stem Cell Reports. Yvonne received her PhD from Frankfurt University and did her postdoctoral work in the laboratory of Henrik Semb at the University of Lund in Sweden. Yvonne is the longest serving member of the journal, serving as Managing Editor since the journal’s inception in 2012. Jack Mosher is the Scientific Advisor for the International Society for Stem Cell Research. He received his PhD from the University of North Carolina in Chapel Hill and was a postdoctoral fellow in the laboratory of Sean Morrison at the University of Michigan. Jack serves numerous roles for the Society including administrative oversight of Stem Cell Reports.  Host Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory X: @martinperaJAX About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Marketing Manager Jack Mosher, Scientific Advisor Hunter Reed, Senior Marketing Coordinator Voice Work Ben Snitkoff

During the last decade, advances in genome editing and pluripotent stem cell (PSC) culture have let researchers generate edited PSC lines to study a wide variety of biological questions. However, abnormalities in cell lines such as aneuploidy, mutations, on-target and off-target editing errors, and microbial contamination can arise during PSC culture or due to undesired editing outcomes. To ensure valid experimental results and the safety of PSC-derived therapeutics, it is important to detect these abnormalities and choose PSC lines without them. Existing quality control methods typically focus on detecting one type of abnormality. Whole genome sequencing is an all-in-one detection method for any abnormality involving changes to DNA sequences but until now it has required considerable computational expertise. Today’s guests will discuss a new computational tool, SeqVerify, that analyzes short-read WGS data for quality control of wild-type or edited PSCs. The platform provides an end-to-end analysis framework that can be a valuable quality control method for researchers working with PSCs, and more broadly, for cell line quality control in general.  Guests George Church, PhD Harvard University, Harvard Medical School, Massachusetts Institute of Technology, and Wyss Harvard Institute. Merrick Smela, PhD, Department of Chemistry and Chemical Biology, Harvard University. Host Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory X: @martinperaJAX Supporting Content SeqVerify: An accessible analysis tool for cell line genomic integrity, contamination, and gene editing outcomes, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Megan Koch, Marketing Manager Jack Mosher, Scientific Advisor Hunter Reed, Senior Marketing Coordinator Voice Work Ben Snitkoff

The ability of human pluripotent and somatic stem cells to differentiate into multiple cell types of the human body makes them uniquely useful to model human development and disease. As a result, these cells are shared, edited, and differentiated by laboratories across the world for basic research, clinical translation, and commercial applications. Large and genotypically diverse collections of pluripotent stem cells are being generated to support large cohort-scale research into conditions such as Parkinson’s disease and amyotrophic lateral sclerosis, among many others. However, information about these cells, their derivatives, and the resulting data can be difficult to track due to a myriad of factors including poor naming practices, siloed datasets, and incomplete information on experimental practices in the published literature. As a result, the ability to maximize the utility of these cells and data from them is limited, and the rigor and reproducibility of the research and its application may be seriously compromised. Our guests today, who were part of the ISSCR Task Force that developed the Standards for the Use of Human Stem Cells in Research, will discuss in detail a framework to manage these issues using stem cell registries.  Guest Andreas Kurtz, PhD, Fraunhofer Institute for Biomedical Engineering and the Berlin Institute of Health Center for Regenerative Therapies  Christine Wells, PhD, University of Melbourne Centre for Stem Cell Systems  Host Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory X: @martinperaJAX Supporting Resources Guidelines for managing and using the digital phenotypes of pluripotent stem cell lines, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Jack Mosher, Scientific Advisor Voice Work Ben Snitkoff

Pluripotent stem cells are defined, in part, by their potential to generate cell types from all three embryonic germ layers. However, it is well known within the field that there is variability in developmental potential between cell lines. This phenomenon, sometimes referred to as lineage bias, is manifest in a variable response of individual cell lines to induction of differentiation into a specific germ layer lineage. Although lineage bias in pluripotent stem cells has been reported for some years, we do not fully understand its molecular basis, or its implications for normal development. The guests on today’s program studied functional variation in human PSC lines as they progress through neurectoderm versus mesendoderm lineages and fore- versus hind-brain development. They will discuss the origin and consequences of inter-individual variation in the early events orchestrating human neural development, the extent to which such variation might impact on adult health and disease, and how it might be exploited in stem cell therapy.  Guests Ron McKay is the Director of Basic Science at the Lieber Institute and has appointments in multiple departments and the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins School of Medicine, USA. He currently serves as a member of the Stem Cell Reports Editorial Board.  Suel-Kee Kim is an Associate Research Scientist in the Department of Neuroscience at Yale University School of Medicine, USA.  Seungmae Seo is an Assistant Professor at University of Maryland Eastern Shore, USA. Seungmae is a former ISSCR Merit and Travel Award Winner. Host Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory @martinperaJAX Supporting Content Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from more than 80 countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Jack Mosher, Scientific Advisor Voice Work Ben Snitkoff

Epigenetic clocks based on tissue DNA methylation analysis have emerged as robust and powerful biomarkers of aging.  This technology has allowed scientists to investigate how diseases affect the aging process, to evaluate the effectiveness of therapeutic aging interventions, and to correlate age with overall health among the general public. Today you can even purchase test kits online that enable you to measure your own biological age.  However, despite the growing use of epigenetic clocks in research, surprisingly little is known about the aging clock’s cellular underpinnings. For example, it remains unclear whether all cells within a tissue exhibit the same epigenetic age, and whether age-related cellular heterogeneity within a tissue affects the epigenetic clock. This is particularly relevant in regenerative tissues maintained by a hierarchy of stem, progenitor, and differentiated cells, all of which may change their frequencies within a tissue with age. The guests on today’s podcast tackle this important question through analyses of immature and mature cell populations from muscle, blood, and epithelia, using three different epigenetic clocks widely used in the field. They discuss their results, and the implications for the interpretation of existing clocks, and the development of more sensitive and accurate clocks.  Guests Konrad Hochedlinger, PhD, Massachusetts General Hospital and Harvard Stem Cell Institute, MA, USA Rebecca Gorelov, PhD, Harvard Medical School, USA Host Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory X: @martinperaJAX Supporting Paper Dissecting the impact of differentiation stage, replicative history, and cell type composition in epigenetic clocks, Stem Cell Reports  About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. X: @StemCellReports About ISSCR With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Jack Mosher, Scientific Advisor Voice Work Ben Snitkoff

Those who study neurological diseases and their underlying cellular and molecular mechanisms have a number of scientific models at their disposal. In vivo animal models, particularly those bearing targeted genetic modifications, remain the gold standard, especially when it comes to assessment of behavioral readouts and neurobiological disease mechanisms in vivo. Historically, animal models have been widely used for preclinical validation of drug efficacy and safety.  Increasingly there is a move away from this approach, and human cellular models using induced pluripotent stem cells and their derivatives such as three-dimensional organoid models have recently provided unprecedented genetic and mechanistic insights into disease mechanisms. Human/animal chimeras made by xenografting human cells into the animal brain have unparalleled potential to study human cells in the context of the whole organism. Our guests today review the use of these types of model systems to understand neuropsychiatric diseases, focusing on Alzheimer’s and Parkinson’s disease, epilepsy, Down syndrome, and schizophrenia and provide critical appraisal of the impact of human-rodent xenografting approaches for advancing our understanding of those diseases and brain development. Host Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory @martinperaJAX Guests Giuseppe Testa, MD, PhD, Università Statale, Human Technopole, and the European Institute of Oncology, Italy Marlene Pereira, PhD UCB Pharma, Brussels, Belgium Reinald Shyti, PhD, Human Technopole and the European Institute of Oncology, Italy Supporting Content In and out: benchmarking in vitro, in vivo, ex vivo and xenografting approaches for an integrative brain disease modeling pipeline, Stem Cell Reports About Stem Cell Reports Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Twitter: @StemCellReports About ISSCR With nearly 5,000 members from 75+ countries, the International Society for Stem Cell Research (@ISSCR) is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. ISSCR Staff Keith Alm, Chief Executive Officer Yvonne Fisher, Managing Editor, Stem Cell Reports Kym Kilbourne, Director of Media and Strategic Communications Jack Mosher, Scientific Advisor Voice Work Ben Snitkoff