Neural stem cell self-renewal is distinct from proliferation of progenitor cells
October 1, 2003
Sarah E Seton-Rogers
Self-renewal of stem cells results in one or both of the daughter cells preserving the properties of the parent cell after division, rather than differentiating, and has important implications for stem cell proliferation and possibly cancer formation as well. The oncogene Bmi-1—a polycomb family transcriptional repressor—is required for maintenance of hematopoietic stem cells, but it has been unclear if Bmi-1 is required for stem cell proliferation or survival. In the October 22 Nature, Anna V. Molofsky, Ricardo Pardal, and colleagues at the University of Michigan report that Bmi-1 is required for self-renewal, as opposed to survival, of neural stem cells. In addition, the authors demonstrate that progenitor cells without stem cell properties do not require Bmi-1 for proliferation (Nature, DOI:10.1038/nature02060, October 22, 2003).
Molofsky, Pardal, et al. examined the capacity for self-renewal of neural stem cells from Bmi-1 null mice and observed that the absence of Bmi-1 resulted in a significant decrease in self-renewal of both central nervous system (CNS) stem cells and gut neural crest stem cells (NCSCs). Analysis of the capacity of the cells to incorporate BrdU indicated that Bmi-1-/-cells proliferated significantly less often than wildtype cells, yet both exhibited similar levels of cell death and similar abilities to proliferate after differentiation. Because lack of Bmi-1 is associated with increased expression of the cyclin-dependent kinase inhibitor p16Ink4a, Molofsky, Pardal, et al. generated Bmi-1-/-p16-/- mice and showed that CNS stem cells and gut NCSCs from these mice displayed increased levels of self-renewal compared with Bmi-1-/- cells, suggesting that Bmi-1 normally inhibits p16Ink4a to fuel self-renewal of these cells. They also examined non-multipotent neural progenitor cells and observed that these cells proliferate normally in the absence of Bmi-1.
“Bmi-1 dependence distinguishes stem cell self-renewal from the proliferation of at least some types of restricted progenitor, providing insight that will help elucidate these pathways further,” conclude the authors.
Links for this article
J. Lessard, G. Sauvageau, “Bmi-1 determines the proliferative capacity
of normal and leukaemic stem cells,” Nature, 423:255-260, May 15, 2003.
I.K. Park et al., “Bmi-1 is required for maintenance of adult self-renewing
haematopoietic stem cells,” Nature, 423:302-305, May 15, 2003.
A.V. Molofsky, R. Pardal, et al., “Bmi-1 dependence distinguishes neural
stem cell self-renewal from progenitor proliferation,” Nature, DOI:10.1038/nature02060,
October 22, 2003.
University of Michigan Medical School
J.J. Jacobs et al., “The oncogene and Polycomb-group gene bmi-1 regulates
cell proliferation and senescence through the ink4a locus,” Nature, 397:164-168,
January 14, 1999.
Copyright © 2003, The Scientist Inc.