The Stem Cell Report with Janet Rossant

Our guests today created new lab models to study Merkel cells using mouse whisker tissue cultures, mouse skin organoids, and human skin organoids. These models allowed them to study Merkel cells as they develop, validate the role of known signaling pathways, and even identify some new ones. Their work provides easier access to Merkel cells for future studies including disease models to understand the pathophysiology of these cells.  

Guests
Ying Xiao, PhD, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China 
Chaochen Wang, PhD...

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...

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...

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...

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...

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...

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...

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...

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 t...

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, it...

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...

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...

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...

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 du...

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 st...

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...

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 m...

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 Cen...

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...

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 mot...

Collectively, retinal degenerative disorders are a major cause of blindness worldwide. For example, one of the most common disorders is age related macular degeneration, which alone affects nearly 200 million globally. 

In humans, and other mammals, the loss of the retinal cells is an irreversible process. However, in some non-mammalian vertebrates like frogs and fish, retinal neurons can regenerate. This process is dependent upon Müller glia, which can re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made in understanding the genetic program underlying these regenerative process, and proof-of-principle ex...

Since the 1930’s research using human fetal tissue has been used in numerous scientific and medical advances that have saved millions of lives, including the development of vaccines and treatments for diseases. Despite its substantial contribution to medicine and science, significant public debate and misinformation persists surrounding the ethical use of human fetal tissue in biomedical research. 

The ISSCR, led by its Public Policy Committee, have been tireless champions and advocates for sound science policy across the globe. This includes advocacy for fetal tissue research and working to inform policymakers and the public on the vast medical app...

This November marks the 25th anniversary of the successful isolation and culture of human embryonic stem cells by Jamie Thompson.  This breakthrough was a turning point in biomedical research. This discovery provided scientists with a limitless source of human cells to understand human biology and model disease. The discovery also provided a novel pathway to develop tissues and cells that could potentially be used to provide curative diseases like diabetes and Parkinson’s, among others. To date, numerous companies are advancing human embryonic stem cell-based therapies in over 50 approved and regulated clinical trials.  

However, in parallel to the...

Human stem cell technology has led to remarkable insights into human biology in health and disease. However, for the results and outputs from this research to be accurate, meaningful, and durable, it is important that the field have agreed upon standards that ensure reproducibility and reliability of the data. The International Society for Stem Cell Research (ISSCR) has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are designed to be technically and financially feasible and, when implemented, to enhance the reproducibility and rigor of stem cell research.  

The guests o...

The use of organoids as an experimental system is rapidly advancing in pace and complexity. Derived from pluripotent or tissue stem cells, organoids are three-dimensional, in vitro, structures intended to model functional or developmental aspects of in vivo organs. They are also being used to model complex physiological systems in organ-on-chip devices and in assembloids, the combination of organoids from different tissues. Organoids are especially useful to model and understand aspects of human biology and pathology. This approach has led to much hope, and proof-of-principle findings, that these structures can serve as human avatars to advance the discovery of...

While teeth have evolved over millions of years, scientists are still working to understand how teeth develop, a process formally known as Odontogenesis. Our guests today have developed a new model of mouse tooth development using long-term expandable 3D tooth organoids from postnatal mouse molars and incisors. This novel mouse model provides a valuable tool to study mouse tooth dental epithelial stem cells, dental epithelial-mesenchymal interactions, and differentiation processes, while allowing further elucidation of tooth type-specific features. These models, in combination with human tooth organoids, have great potential to further unravel tooth biology and repair and may be an...

Over the last 10 years of Stem Cell Reports, the journal has published nearly 2,000 papers across the breadth of stem cell research. In this special episode of the podcast, we are celebrating the anniversary of the journal by talking with the authors from some of the most highly cited publications in the journal's history.

The guests on this episode of the podcast have collective expertise that makes them the “dream team” of muscle stem cell biology and its application to treat disease.  

 Akitsu Hotta is a Principal Investigator and Associate Professor in the Department of Cli...

Human pluripotent stem cells have an unlimited capacity to self-renew in culture. This feature, along with their ability to become any cell type in the adult body, makes them a unique tool to study human biology in health and disease. Unfortunately, human pluripotent stem cells have a propensity to acquire genetic abnormalities in culture that may limit their scientific and clinical use.

Among the most prevalent genomic changes found in pluripotent stem cells are various forms of over-representation of sequences on the long arm of chromosome 20, with up to 20% of tested cultures containing such an aberration. One...

The PiWi family of genes may have a diminutive sounding name, but they have a large role in the function of the germline and germline stem cells. Initially discovered in Drosophila, these highly conserved RNA-binding proteins have well-established roles in the regulation of spermatogenesis and germ stem cell maintenance, in addition to silencing transposable elements. However, PiWi function outside of the germline is relatively unexplored. New findings from the Lin laboratory show that Drosophila Piwi has a role in intestinal homeostasis where it functions to establish intestinal stem cells, maintain the enteroblast lineage, and support of the enterocytes. It...

This episode is sponsored by Bio-Techne.

While advances in stem cell science have led to an increasing number of stem cell-based therapies entering clinical trials, the field is still relatively immature. Thus, these first-in-human trials are using pioneering approaches unique unto themselves, leaving scientists, physicians, and regulators to assess the best approaches for a specific therapy and/or disease.  In this episode of the podcast, Martin Pera is joined by physician-scientists Roger Barker and Rajesh Rao who have and are leading stem cell-based trials to discuss some of the critical aspects of the process and reflect on t...

This episode is sponsored by Bio-Techne.

Computational approaches have become integral to understanding biological processes, in part because of a need to come to grips with the enormous amounts of high dimensional data that we generate using our current tools for cellular analysis. This is especially relevant for stem cell and developmental biology where development, disease modeling, regulatory networks, and lineage formation all lend themselves to the combination of experimental and computational methods. Today’s program explores how computational biology approaches can be used to understand and model early development, specifically the lineage commitment of the early em...

This episode of The Stem Cell Report will explore the scientific applications, advances, and challenges of interspecies chimeras – organisms consisting of cells from at least two different species. The development of interspecies chimeras, most recently advanced by the discovery of pluripotent stem cells and enhancements in genetic editing, have led to greater understanding of fundamental developmental and biological concepts, insight into evolution, and even the development of potential regenerative approaches for human health. Martin Pera will be joined by Drs. Ori Bar-Nur and Jun Wu, along with Joel Zvick, next generation scientists who are pioneering advances in interspecies chimera re...

In this episode of The Stem Cell Report, sponsored by Bio-Techne, we will explore the modeling of complex human neuropsychiatric diseases such as autism, bipolar disorder, and others using stem cell-based, three-dimensional culture models of the brain and its development. Martin Pera will be joined by Drs. Carol Marchetto and Rusty Gage, experts in the normal and pathological development of the brain. Carol Marchetto is an Assistant Professor in the Anthropology Department at the University of California, San Diego and an adjunct Assistant Professor at the Salk Institute. Rusty Gage is the Vi and John Adler Chair for Research...

To celebrate the ISSCR’s 20th anniversary, Martin Pera is joined by three members of the ISSCR Board of Directors; Fiona Doetsch (Biozentrum at the University of Basel, Switzerland), Clerk of the ISSCR, Takanori Takebe (Cincinnati Children's Hospital Medical Center, USA/Tokyo Medical and Dental University and Yokohama City University, Japan) is a Director, and Leonard Zon (Boston Children’s Hospital, USA) is an Ex Officio member, past president, and founder of the ISSCR. In addition to running their own laboratories these scientists are part of the ISSCR leadership and will talk about the ISSCR’s history, impact, the recent...

In this episode of The Stem Cell Report, Martin Pera is joined by three experts on the eye, its development, and disease processes.  Dr. Mark Humayun is the Director of the Institute for Biomedical Therapeutics and Co-Director of the Roski Eye Institute at the University of Southern California.  Dr. Anand Swaroop is a Senior Investigator in the Neurobiology, Neurodegeneration and Repair Laboratory at the National Eye Institute, and Dr. Masayo Takahashi is a pioneer in iPS-based approaches to treat eye disease and the President of Vision Care Inc., a venture that will focus on cell-based treatments for macular de...

In this episode of The Stem Cell Report, Martin Pera is joined by Douglas Melton, a pioneer in the use of stem cell-based transplants to treat Type 1 diabetes, and Nayara Leite, a former postdoc in the Melton laboratory who now works for Vertex Pharmaceuticals, one of the companies currently testing stem cell-derived transplants for diabetes in clinical trials. Drs. Melton and Leite will talk about the concepts and issues around stem cell-based treatments for diabetes and their new paper that looks at ways to enhance the survival and function of the insulin producing islets.

Guests<...

In this episode of the Stem Cell Report, Martin Pera is joined by a team of scientists from the Neural Stem Cell Institute in Rensselaer, NY, USA.  Drs. Elizabeth Fisher, Xiuli Zhao, and Institute Director Sally Temple talk about their new paper on neural stem and progenitor cell function in the aging adult brain. They use live time-lapse imaging with computer-based image analysis to assess young and aged neural stem and progenitor cells in 3D brain structures to assess the mechanism underlying changes to the aging brain. 

Guests
Sally Temple, PhD, Neural Stem Cell In...

In this episode, Drs. Shimpei Gotoh, Takahiro Suezawa, and Carla Kim join the podcast to talk about using stem and progenitor cells to understand the adult lung and model disease processes impacting lung function. Their research and discoveries provide insight into lung homeostasis, the potential for regeneration, and understanding diseases like pulmonary fibrosis and cancer.

Drs. Gotoh and Suezawa are two of the authors of the recent paper ”Disease modeling of pulmonary fibrosis using human pluripotent stem cell-derived alveolar organoids” in Stem Cell Reports. Dr Kim is a member of the Stem Cell Reports Editorial Board and an e...

In this episode, Drs. Fiona Watt and Alice Vickers join the podcast to talk about uncovering the relationship between genetic variants and cellular behavior. They recently developed a platform to quantify iPSC differentiation propensity to investigate the genetic contribution to phenotypic variability. Drs. Vickers and Watt are authors of the recent paper,  "Plating human iPSC lines on micropatterned substrates relevels role for ITGBI nsSNV in endoderm formation” in Stem Cell Reports. 

Guests
Fiona Watt, DPhil, Centre for Stem Cells and Regenerative Medicine, King’s College London
Website: http://www.wattlab.org/ 

Alice V...

In this episode Drs. Charles Murry and Kenta Nakamura join the podcast to talk about “cardiac remuscularization therapy,” and the general approach of transplanting human pluripotent stem cell-derived cardiomyocytes to restore cardiac function after injury.

Guests
Charles Murry, MD, PhD, University of Washington and Sana Biotechnology
Kenta Nakamura, MD, University of Washington and VA Puget Sound Healthcare System 

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

Supporting Document
Drs. Murry and Nakamura are two of the authors...