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, Scho...

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 accompli...

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 b...

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 neurotransmit...

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 ...

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 v...

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...

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 so...

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...

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 ...

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 reprog...

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. ...