Topic
Neurosphere
About: Neurosphere is a research topic. Over the lifetime, 5145 publications have been published within this topic receiving 321088 citations.
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TL;DR: It is reported that in activation of Hes1 and Hes5, known Notch effectors, and additional inactivation of Hes3 extensively accelerate cell differentiation and cause a wide range of defects in brain formation.
Abstract: Radial glial cells derive from neuroepithelial cells, and both cell types
are identified as neural stem cells. Neural stem cells are known to change
their competency over time during development: they initially undergo
self-renewal only and then give rise to neurons first and glial cells later.
Maintenance of neural stem cells until late stages is thus believed to be
essential for generation of cells in correct numbers and diverse types, but
little is known about how the timing of cell differentiation is regulated and
how its deregulation influences brain organogenesis. Here, we report that
inactivation of Hes1 and Hes5 , known Notch effectors, and
additional inactivation of Hes3 extensively accelerate cell
differentiation and cause a wide range of defects in brain formation. In
Hes -deficient embryos, initially formed neuroepithelial cells are not
properly maintained, and radial glial cells are prematurely differentiated
into neurons and depleted without generation of late-born cells. Furthermore,
loss of radial glia disrupts the inner and outer barriers of the neural tube,
disorganizing the histogenesis. In addition, the forebrain lacks the optic
vesicles and the ganglionic eminences. Thus, Hes genes are essential
for generation of brain structures of appropriate size, shape and cell
arrangement by controlling the timing of cell differentiation. Our data also
indicate that embryonic neural stem cells change their characters over time in
the following order: Hes -independent neuroepithelial cells,
transitory Hes -dependent neuroepithelial cells and
Hes -dependent radial glial cells.
573 citations
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TL;DR: Evidence is presented that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo, and this capacity of committed cells to dedifferentiate into stem cells may have a more general role in the regeneration of many tissues and in multiple disease states, notably cancer.
Abstract: Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. Here we present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts in repairing epithelial injury. Single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. By contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate is inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may have a more general role in the regeneration of many tissues and in multiple disease states, notably cancer.
571 citations
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TL;DR: Stem cells can be isolated from hippocampus-adjacent regions of subependyma, but the adult DG proper does not contain a population of resident neural stem cells, suggesting that neuron-specific progenitors and not multipotential stem cells are the source of newly generated DG neurons throughout adulthood.
Abstract: Neurogenesis persists in two adult brain regions: the ventricular subependyma and the subgranular cell layer in the hippocampal dentate gyrus (DG). Previous work in many laboratories has shown explicitly that multipotential, self-renewing stem cells in the subependyma are the source of newly generated migrating neurons that traverse the rostral migratory stream and incorporate into the olfactory bulb as interneurons. These stem cells have been specifically isolated from the subependyma, and their properties of self-renewal and multipotentiality have been demonstrated in vitro. In contrast, it is a widely held assumption that the “hippocampal” stem cells that can be isolated in vitro from adult hippocampus reside in the neurogenic subgranular layer and represent the source of new granule cell neurons, but this has never been tested directly. Primary cell isolates derived from the precise microdissection of adult rodent neurogenic regions were compared using two very different commonly used culture methods: a clonal colony-forming (neurosphere) assay and a monolayer culture system. Importantly, both of these culture methods generated the same conclusion: stem cells can be isolated from hippocampus-adjacent regions of subependyma, but the adult DG proper does not contain a population of resident neural stem cells. Indeed, although the lateral ventricle and other ventricular subependymal regions directly adjacent to the hippocampus contain neural stem cells that exhibit long-term self-renewal and multipotentiality, separate neuronal and glial progenitors with limited self-renewal capacity are present in the adult DG, suggesting that neuron-specific progenitors and not multipotential stem cells are the source of newly generated DG neurons throughout adulthood.
557 citations
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TL;DR: The properties of the hES-derived progenitors and neurons were found to be similar to those of cells derived from primary tissue and indicate that hES cells could provide a cell source for the neural progenitor cells and mature neurons for therapeutic and toxicological uses.
556 citations
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TL;DR: It is shown that the adult human brain harbors a complex population of stem/progenitor cells that can generate neuronal and glial progeny under particular in vitro growth conditions.
556 citations