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G. Bernier, W. Chatoo, M. Abdouh; Bmi1 Dependency and Expression Levels Distinguishes Retinal Progenitor/Stem Cells From the Main Retinal Progenitor Cell Population. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1287.
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© ARVO (1962-2015); The Authors (2016-present)
The developing mammalian retina is generated by the proliferation and expansion of multipotent retinal progenitor cells (RPCs) giving rise to all neuronal and glial cell types. We previously reported on the isolation of a rare RPC population present in the mouse optic vesicle showing stem cell characteristic. The purpose of this study is to evaluate if stem-like cells are present in the developing mouse retina and whether they are distinct from the main RPC population.
To isolate and characterize distinct RPC populations in the developing mouse retina, we used the CD133, SSEA1 and Bmi1 antibodies to perform cell-sorting analyses. Purified cells were tested for colony formation using the neurosphere assay, and analyzed for gene expression by Real-time PCR. Retinas from wild type and Bmi1-null embryos and mice were used to perform neurosphere assays.
The Polycomb group and oncogene Bmi1 is expressed at low levels in most RPCs and at high levels in a CD133+/SSEA-1high RPC sub-population. The Bmi1high RPC sub-population represents about 4% of all retinal cells at e12.5 and is enriched 10-30 times for expression of the stem cell markers Musashi, Sox2 and Lhx2. Cell sorting and neurosphere assays revealed that the colony-forming unit of the embryonic retina is predominantly contained within the Bmi1high RPC sub-population. Bmi1 deficiency results in reduction of cell proliferation at the retinal ciliary margin in vivo and loss of stem/progenitor cell self-renewal capacity in vitro. In contrast, Bmi1 deficiency minimally affects proliferation of the main RPC population in vivo and in vitro.
Our results suggest that the developing mammalian retina contains a rare stem/progenitor cell population distinct from the main RPC population and genetically defined by Bmi1 expression level and dependency.
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