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