Bmi-1 cooperates with Foxgl to maintain neural stem cell self-renewal in the forebrain Journal Article
| Authors: | Fasano, C. A.; Phoenix, T. N.; Kokovay, E.; Lowry, N.; Elkabetz, Y.; Dimos, J. T.; Lemischka, I. R.; Studer, L.; Temple, S. |
| Article Title: | Bmi-1 cooperates with Foxgl to maintain neural stem cell self-renewal in the forebrain |
| Abstract: | Neural stem cells (NSCs) persist throughout life in two forebrain areas: the subventricular zone (SVZ) and the hippocampus. Why forebrain NSCs self-renew more extensively than those from other regions remains unclear. Prior studies have shown that the polycomb factor Bmi-1 is necessary for NSC self-renewal and that it represses the cell cycle inhibitors pl6, pl9, and p21. Here we show that overexpression of Bmi-1 enhances self-renewal of forebrain NSCs significantly more than those derived from spinal cord, demonstrating a regional difference in responsiveness. We show that forebrain NSCs require the forebrain-specific transcription factor Foxgl for Bmi-1-dependent self-renewal, and that repression of p21 is a focus of this interaction. Bmi-1 enhancement of NSC self-renewal is significantly greater with increasing age and passage. Importantly, when Bmi-1 is overexpressed in cultured adult forebrain NSCs, they expand dramatically and continue to make neurons even after multiple passages, when control NSCs have become restricted to glial differentiation. Together these findings demonstrate the importance of Bmi-1 and Foxgl cooperation to maintenance of NSC multipotency and self-renewal, and establish a useful method for generating abundant forebrain neurons ex vivo, outside the neurogenic niche. © 2009 by Cold Spring Harbor Laboratory Press. |
| Keywords: | controlled study; unclassified drug; oncoprotein; proto-oncogene proteins; nonhuman; cell proliferation; forkhead transcription factors; animal cell; mouse; animal; cytology; metabolism; animals; mice; animal tissue; cell survival; cells, cultured; gene overexpression; gene expression; nuclear protein; animal experiment; brain cortex; nerve tissue proteins; transcription factor; cell renewal; neural stem cell; subventricular zone; adult stem cells; stem cell; nuclear proteins; prenatal development; cell culture; gene interaction; spinal cord; gene repression; stem cells; pregnancy; cerebral cortex; protein p21; bmil; neural stem cells; self-renewal; svz; bmi1 protein; transcription factor foxg1; bmi1 protein, mouse; forkhead transcription factor; foxg1 protein, mouse; nerve protein; repressor protein; forebrain; multipotent stem cell; nerve cell differentiation; prosencephalon; repressor proteins |
| Journal Title: | Genes and Development |
| Volume: | 23 |
| Issue: | 5 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2009-03-01 |
| Start Page: | 561 |
| End Page: | 574 |
| Language: | English |
| DOI: | 10.1101/gad.1743709 |
| PUBMED: | 19270157 |
| PROVIDER: | scopus |
| PMCID: | PMC2658524 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 30 November 2010" - "CODEN: GEDEE" - "Source: Scopus" |
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