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© The Rockefeller University Press, 0021-9525/2003/11/435 $8.00
The Journal of Cell Biology, Volume 163, Number 3, 435-435

How to renew a stem cell

Stem cells lacking Bmi-1 proliferate poorly. Morrison/Macmillan

The unique cell cycle characteristics of stem cells are defined, at least in part, by a polycomb transcription factor called Bmi-1, according to Anna Molofsky, Ricardo Pardal, Sean Morrison, and colleagues (University of Michigan, Ann Arbor, MI). Bmi-1 is unique because, unlike other important cell cycle proteins such as Myc, it is needed in stem cells but not in their offspring. Thus, it is important as much for what it is not as for what it is.

The loss of Bmi-1, the researchers find, leaves mice deficient in stem cell capacity. The mice survive using only restricted progenitor cells that are limited in both the types of cells that they can generate and the numbers of divisions in which they can do so. The resulting depletion in cells leads to growth and neurological defects, and early death.

Earlier work had established that Bmi-1, via its repression of the cell cycle inhibitor p16, is required for the proliferation of hematopoietic stem cells (HSCs). The Michigan group found a similar phenomenon with stem cells in the central nervous system, at least after birth, and found that the cause was reduced proliferation rather than increased cell death. But after differentiation factors were added, the difference disappeared. Now, both cells with and without Bmi-1 continued to proliferate.

There are two situations in which an explanation requires more than just Bmi-1 and p16. Prenatally, something other than Bmi-1 must be capable of repressing p16 expression. In the restricted progenitors, meanwhile, Bmi-1 is no longer needed because the cell cycle is now insensitive to elevated levels of p16. Future studies will be focused on understanding this difference in sensitivity, and testing downstream of Bmi-1 for pathways unrelated to p16.

Reference:

Molofsky, A.V., et al. 2003. Nature. 10.1038/nature02060.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 691K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?