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In vitro generation of early-born neurons from late retinal progenitors.

ABSTRACT: Evidence suggests that, as development ensues, the competence of neural progenitors is progressively altered, such that they become fated to give rise to neurons of a particular stage. Here, we demonstrate that late retinal progenitors can give rise to retinal ganglion cells (RGCs), an example of an early-born cell type in the retina. A subset of late retinal progenitors in vitro responds to cues that favor RGC differentiation by displaying markers characteristic of RGCs. In addition, mechanisms used during normal RGC differentiation are recruited by these cells toward their differentiation along RGC lineage. Our observations suggest that late neural progenitors may not be irreversibly fated but may appear as such under the constraints dictated by epigenetic cues.

SUBMITTER: James J

PROVIDER: S-EPMC6740685 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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In vitro generation of early-born neurons from late retinal progenitors.

James Jackson J Das Ani V AV Bhattacharya Sumitra S Chacko David M DM Zhao Xing X Ahmad Iqbal I

The Journal of neuroscience : the official journal of the Society for Neuroscience 20030901 23

Evidence suggests that, as development ensues, the competence of neural progenitors is progressively altered, such that they become fated to give rise to neurons of a particular stage. Here, we demonstrate that late retinal progenitors can give rise to retinal ganglion cells (RGCs), an example of an early-born cell type in the retina. A subset of late retinal progenitors in vitro responds to cues that favor RGC differentiation by displaying markers characteristic of RGCs. In addition, mechanisms ...[more]

PMID: 12967980

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Project description:The neural stem cells discovered in the adult ciliary epithelium (CE) in higher vertebrates have emerged as an accessible source of retinal progenitors; these cells can self-renew and possess retinal potential. However, recent studies have cast doubt as to whether these cells could generate functional neurons and differentiate along the retinal lineage. Here, we have systematically examined the pan neural and retinal potential of CE stem cells.Molecular and cellular analysis was carried out to examine the plasticity of CE stem cells, obtained from mice expressing green fluorescent protein (GFP) under the influence of the promoter of the rod photoreceptor-specific gene, Nrl, using the neurospheres assay. Differentiation was induced by specific culture conditions and evaluated by both transcripts and protein levels of lineage-specific regulators and markers. Temporal pattern of their levels were examined to determine the expression of genes and proteins underlying the regulatory hierarchy of cells specific differentiation in vitro. Functional attributes of differentiation were examined by the presence of current profiles and pharmacological mobilization of intracellular calcium using whole cell recordings and Fura-based calcium imaging, respectively. We demonstrate that stem cells in adult CE not only have the capacity to generate functional neurons, acquiring the expression of sodium and potassium channels, but also respond to specific cues in culture and preferentially differentiate along the lineages of retinal ganglion cells (RGCs) and rod photoreceptors, the early and late born retinal neurons, respectively. The retinal differentiation of CE stem cells was characterized by the temporal acquisition of the expression of the regulators of RGCs and rod photoreceptors, followed by the display of cell type-specific mature markers and mobilization of intracellular calcium.Our study demonstrates the bonafide retinal potential of adult CE stem cells and suggests that their plasticity could be harnessed for clinical purposes once barriers associated with any lineage conversion, i.e., low efficiency and fidelity is overcome through the identification of conducive culture conditions.

Dataset Information

In vitro generation of early-born neurons from late retinal progenitors.

Publications

In vitro generation of early-born neurons from late retinal progenitors.

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