The Stem Cell Report with Janet Rossant

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