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- Title
Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells.
- Authors
Hock, Hanno; Hamblen, Melanie J.; Rooke, Heather M.; Schindler, Jeffrey W.; Saleque, Shireen; Fujiwara, Yuko; Orkin, Stuart H.
- Abstract
Haematopoietic stem cells (HSCs) sustain blood production throughout life. HSCs are capable of extensive proliferative expansion, as a single HSC may reconstitute lethally irradiated hosts. In steady-state, HSCs remain largely quiescent and self-renew at a constant low rate, forestalling their exhaustion during adult life. Whereas nuclear regulatory factors promoting proliferative programmes of HSCs in vivo and ex vivo have been identified, transcription factors restricting their cycling have remained elusive. Here we report that the zinc-finger repressor Gfi-1 (growth factor independent 1), a cooperating oncogene in lymphoid cells, unexpectedly restricts proliferation of HSCs. After loss of Gfi-1, HSCs display elevated proliferation rates as assessed by 5-bromodeoxyuridine incorporation and cell-cycle analysis. Gfi-1-/- HSCs are functionally compromised in competitive repopulation and serial transplantation assays, and are rapidly out-competed in the bone marrow of mouse chimaeras generated with Gfi-1-/- embryonic stem cells. Thus, Gfi-1 is essential to restrict HSC proliferation and to preserve HSC functional integrity.
- Subjects
HEMATOPOIETIC stem cells; STEM cells; EMBRYONIC stem cells; BONE marrow cells; BONE marrow; CELL proliferation
- Publication
Nature, 2004, Vol 431, Issue 7011, p1002
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature02994