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