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- Title
Bmi1 Distinguishes Immature Retinal Progenitor/Stem Cells from the Main Progenitor Cell Population and Is Required for Normal Retinal Development.
- Authors
Chatoo, Wassim; Abdouh, Mohamed; Duparc, Robert-Hiigues; Bernikr, Gilbert
- Abstract
The developing mammalian retina is generated by the proliferation and differentiation of multipotent retinal progenitor cells (RPCs) giving rise to neuronal and glial lineages. Whether an immature progenitor/stem cell subpopulation is present in the developing mammalian retina remains undefined. Deficiency in the polycomh group gene Bmi1 results in reduced proliferation and postnatal depletion of neural and hematopoietic stem cells. Here, we show that Bmi1 is required for the self-renewal of most immature RPCs and for postnatal retinal development. In the embryo., Bmi1 is highly enriched in a rare stage-specific emhryonic antigen-1-positive RPC subpopulation expressing the stem cell markers Sox2, Lhx2., and Musashi. Gain-of- function experiments revealed that Bmi1 overexpression could convert RPCs having limited proliferation capacity into RPCs showing extensive proliferation and multiple differentiation capacities over time. At all developmental stages analyzed using the neurosphere assay, Bmi1 deficiency resulted in reduced proliferation and self-renewal of most immature RPCs. Reduced RPCs proliferation was also observed in the peripheral retina of Bmi1-1- fetus and newborn mice. The biological impact of these developmental anomalies was revealed by the reduced retinal diameter of Bmi1-deficient pups. P19Arf and p16Ink4a were upregulated in vivo and in vitro and coinactivation of p53, which lies downstream of p19Arf, partially restored Bmi1 deficient RPCs self-renewal phenotype. Bmil thus distinguishes immature RPCs from the main RPC population and is required for normal retinal development.
- Subjects
ALTERNATIVE treatment for retinal degeneration; HEMATOPOIETIC stem cell transplantation; MOLECULAR cloning; HEMATOPOIETIC stem cells; CELL proliferation -- Molecular aspects; EYE surgery instruments industry; THERAPEUTICS
- Publication
Stem Cells, 2010, Vol 28, Issue 8, p1412
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.462