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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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Journal ArticleDOI
TL;DR: Interference with Notch signaling provides a tool for controlling human NSC differentiation both in vitro and in vivo.
Abstract: The controlled in vitro differentiation of human embryonic stem cells (hESCs) and other pluripotent stem cells provides interesting prospects for generating large numbers of human neurons for a variety of biomedical applications. A major bottleneck associated with this approach is the long time required for hESC-derived neural cells to give rise to mature neuronal progeny. In the developing vertebrate nervous system, Notch signaling represents a key regulator of neural stem cell (NSC) maintenance. Here, we set out to explore whether this signaling pathway can be exploited to modulate the differentiation of hESC-derived NSCs (hESNSCs). We assessed the expression of Notch pathway components in hESNSCs and demonstrate that Notch signaling is active under self-renewing culture conditions. Inhibition of Notch activity by the gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) in hESNSCs affects the expression of human homologues of known targets of Notch and of several cell cycle regulators. Furthermore, DAPT-mediated Notch inhibition delays G1/S-phase transition and commits hESNSCs to neurogenesis. Combined with growth factor withdrawal, inhibition of Notch signaling results in a marked acceleration of differentiation, thereby shortening the time required for the generation of electrophysiologically active hESNSC-derived neurons. This effect can be exploited for neural cell transplantation, where transient Notch inhibition before grafting suffices to promote the onset of neuronal differentiation of hESNSCs in the host tissue. Thus, interference with Notch signaling provides a tool for controlling human NSC differentiation both in vitro and in vivo.

205 citations

Book ChapterDOI
TL;DR: One of the key advances in the field of neurobiology is the discovery that astroglial cells can generate neurons not only during development, but also throughout adult life and potentially even after brain lesion.
Abstract: Astroglial cells are the most frequent cell type in the adult mammalian brain, and the number and range of their diverse functions are still increasing. One of their most striking roles is their function as adult neural stem cells and contribution to neurogenesis. This chapter discusses first the role of the ubiquitous glial cell type in the developing nervous system, the radial glial cells. Radial glial cells share several features with neuroepithelial cells, but also with astrocytes in the mature brain, which led to the name "radial glia." At the end of neurogenesis in the mammalian brain, radial glial cells disappear, and a subset of them transforms into astroglial cells. Interestingly, only some astrocytes maintain their neurogenic potential and continue to generate neurons throughout life. We discuss the current knowledge about the differences between the adult astroglial cells that remain neurogenic and act as neural stem cells and the majority of other astroglial cells that have apparently lost the capacity to generate neurons. Additionally, we review the changes in glial cells upon brain lesion, their dedifferentiation and recapitulation of radial glial properties, and the conditions under which reactive glia may reinitiate some neurogenic potential. Given that the astroglial cells are not only the most frequent cell type in an adult mammalian brain, but also the key cell type in the wound reaction of the brain to injury, it is essential to further understand their heterogeneity and molecular specification, with the final aim of using this unique source for neuronal replacement. Therefore, one of the key advances in the field of neurobiology is the discovery that astroglial cells can generate neurons not only during development, but also throughout adult life and potentially even after brain lesion.

204 citations

Journal ArticleDOI
TL;DR: Evidence is presented that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in theadult subventricular zone.
Abstract: Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.

203 citations

PatentDOI
TL;DR: In this paper, a method of generating neural crest stem cells involves inducing neuroepithelial stem cells to differentiate in vitro into neural crest cells, which can be induced by replating the cells on laminin, withdrawing mitogens, or adding dorsalizing agents to the growth medium.

203 citations

Journal ArticleDOI
20 Feb 2008-PLOS ONE
TL;DR: The SD56 human neural stem cells derived under the reported conditions are stable, do not form tumors in vivo and enable functional recovery after stroke, indicating that this hNSC line may offer a renewable, homogenous source of neural cells that will be valuable for basic and translational research.
Abstract: Background Human embryonic stem cells (hESCs) offer a virtually unlimited source of neural cells for structural repair in neurological disorders, such as stroke. Neural cells can be derived from hESCs either by direct enrichment, or by isolating specific growth factor-responsive and expandable populations of human neural stem cells (hNSCs). Studies have indicated that the direct enrichment method generates a heterogeneous population of cells that may contain residual undifferentiated stem cells that could lead to tumor formation in vivo. Methods/Principal Findings We isolated an expandable and homogenous population of hNSCs (named SD56) from hESCs using a defined media supplemented with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and leukemia inhibitory growth factor (LIF). These hNSCs grew as an adherent monolayer culture. They were fully neuralized and uniformly expressed molecular features of NSCs, including nestin, vimentin and radial glial markers. These hNSCs did not express the pluripotency markers Oct4 or Nanog, nor did they express markers for the mesoderm or endoderm lineages. The self-renewal property of the hNSCs was characterized by a predominant symmetrical mode of cell division. The SD56 hNSCs differentiated into neurons, astrocytes and oligodendrocytes throughout multiple passages in vitro, as well as after transplantation. Together, these criteria confirm the definitive NSC identity of the SD56 cell line. Importantly, they exhibited no chromosome abnormalities and did not form tumors after implantation into rat ischemic brains and into naive nude rat brains and flanks. Furthermore, hNSCs isolated under these conditions migrated toward the ischemia-injured adult brain parenchyma and improved the independent use of the stroke-impaired forelimb two months post-transplantation. Conclusions/Significance The SD56 human neural stem cells derived under the reported conditions are stable, do not form tumors in vivo and enable functional recovery after stroke. These properties indicate that this hNSC line may offer a renewable, homogenous source of neural cells that will be valuable for basic and translational research.

202 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
2023131
2022140
2021121
2020121
2019124