Human pluripotent stem cells (hPSCs) are transforming the study of biology and disease by enabling scientists to grow large amounts of specific cell types in the lab that were once difficult to obtain. Our guests today focus on improving the derivation and study of sensory neurons, which are sparse and diverse nerve cells near the spine that carry information like pain, touch, or position of the body to the brain. Damage to these neurons or sensory neuropathies, as can happen in diabetes or infections, is estimated to affect millions of people worldwide, yet treatments are limited. To improve the generation of human sensory neurons, the authors developed a genetic toolkit to fluorescently label these individual cells and their subtypes. This approach enables more precise study of these subtypes, their roles in disease, and potentially the development of treatments for sensory neuropathies.

Guests
Joriene C. de Nooij, PhD, Department of Neurology, Columbia University, USA
Eti Malka-Gibor, PhD, Department of Neurology, Columbia University, USA

Host
Janet Rossant, Editor-in-Chief, Stem Cell Reports and The Gairdner Foundation

Supporting Content
Paper link: Derivation and analysis of human somatic sensory neuron subtypes facilitated through fluorescent hPSC reporters," 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

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