The Stem Cell Report with Janet Rossant – Détails, épisodes et analyse

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

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

This episode of The Stem Cell Report will discuss the process of directing stem cells to acquire the proper identity, an essential step in the development of effective and durable cell replacement therapies. Specifically, we will talk about the process of directing cells into a ventral mesencephalic dopaminergic fate for treating Parkinson’s disease. 

Guests
Agnete Kirkeby is an Associate Professor in the Department of Neuroscience at the University of Copenhagen, a Principal Investigator with the Novo Nordisk Foundation Center for Stem Cell Medicine renew, and a Principal Investigator at the Wallenberg Center for Molecular Medicine at Lund University. Professor Kirkeby led the preclinical development of a stem cell-based therapy for Parkinson’s Disease which was approved for a first-in-human clinical trial in Sweden. Agnete also co-chairs the ISSCR 2024 Annual Meeting Program Committee, the group responsible for planning the upcoming meeting this July in Hamburg, Germany. 

Pedro Rifes received his PhD from the Universidade de Lisboa in Portugal and was a postdoctoral scholar in the Kirkeby Laboratory. He served as an Adjunct Assistant Professor at the University of Copenhagen and is currently a Project Manager at Bioneer A/S, a Danish specialty Contract Research Organization.  Connect with him on LinkedIn.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Supporting Content
Paper link: Forced LMX1A expression induces dorsal neural lolfates and disrupts patterning of human embryonic stem cells into ventral midbrain dopaminergic neurons, 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 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 

Myelination is one of the last events during mammalian brain development and is thought to continue into young adulthood in humans. Even in adulthood, ongoing low-level myelination is essential for neural homeostasis, and for dynamic processes such as learning and memory. Deficits in myelination resulting in abnormal white matter and disruption of neuronal function are observed in a wide variety of disorders of the CNS. One strategy for alleviating these deficits is to enhance the genesis of myelin-forming oligodendrocytes from their upstream precursor parents, oligodendrocyte precursor cells (OPCs). However, the capability of these OPCs to contribute to remyelination in injury or disease in the adult CNS remains unclear.  To better understand adult oligodendrogenesis and remyelination, our guests today characterized and compared murine OPCs during early postnatal myelination with those from adult injury-induced adult remyelination. Their findings identify two developing OPC groups subserving distinct postnatal functions and suggest that neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different, The findings have important implications for therapeutic interventions aimed at myelin repair. 

Guests
Freda Miller, PhD, Michael Smith Laboratories, The University of British Columbia
Beatrix Wang, BSC, PhD candidate, The University of British Columbia and The University of Toronto

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Supporting Content
Single-cell approaches define two groups of mammalian oligodendrocyte precursor cells and their evolution over developmental time, 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 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 

Biomedical researchers have long sought ways to repair spinal cord damage with the holy grail of the pursuit being the reconstitution of lost function. In the mid 1990’s with the successful culture of human embryonic stem cells, and about a decade later induced pluripotent stem cells (iPSCs), the field was energized with a potential new approach to replace the lost neurons and glia cells and restoring neural connections.  In the decades since that discovery some progress has been made, however many hurdles remain, including establishing a functional synaptic connection between the transplanted and host neurons which is crucial for motor function recovery. To boost therapeutic outcomes our guests tested an ex vivo gene therapy to promote synapse formation between the donor and host neurons by expressing the synthetic excitatory synapse organizer CPTX in hiPSCs-derived neural stem and progenitor cells. Tune in to learn what they discovered.

Host
Martin Pera, Editor-in-Chief, Stem Cell Reports and The Jackson Laboratory
@martinperaJAX

Guests
Hideyuki Okano, MD, PhD Keio University, Japan, Professor in the Department of Physiology and Chairman of the Graduate School of Medicine at Keio University. Professor Okano has spent decades studying neurogenesis and is currently leading a first-of-its-kind cell therapy for spinal cord injury. He has previously served as an Associate Editor for Stem Cell Reports and is a member of the Editorial Board. He is the current President of the Japanese Society of Regenerative Medicine and Vice President of the ISSCR. 
 
Yusuke Saijo, MD. Keio University, Japan, graduated from Kyorin University School of Medicine and following a two-year initial training period, he embarked on a clinical journey, working in the field of orthopedic surgery at Keio University, specializing in the spinal cord and spinal disorders. Dr. Yusuke currently works in the research laboratory led by Professors Okano and Masaya Nakamura, where his research focuses on ex vivo cell and gene therapy for spinal cord regeneration. 

Supporting Content
Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury, 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, Scien