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Transcription factor Gfi1 regulates self‐renewal and engraftment of hematopoietic stem cells
Author(s) -
Zeng Hui,
Yücel Raif,
Kosan Christian,
KleinHitpass Ludger,
Möröy Tarik
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600419
Subject(s) - biology , transcription factor , haematopoiesis , stem cell , microbiology and biotechnology , genetics , hematopoietic stem cell , transcription (linguistics) , cancer research , gene , linguistics , philosophy
The generation of all blood cells depends on the ability of hematopoietic stem cells (HSCs) for self‐renewal and multilineage differentiation. We show here that the transcription factor Gfi1 is expressed in HSCs and in more mature cells such as common lymphoid progenitors (CLPs) and granulo/monocytic progenitors, but is absent in common myeloid progenitors and megakaryocyte/erythroid progenitors. When Gfi1 is deleted in mice, HSC frequencies are significantly reduced and CLPs all but disappear from the bone marrow. This specific requirement of Gfi1 for the maintenance of HSC numbers is cell autonomous. Transplantation of Gfi1‐deficient bone marrow results in a compromised radioprotection and lower numbers of colony forming units in the spleen of wild‐type recipients. Strikingly, Gfi1 −/− bone marrow cells are severely impaired in competitive long‐term reconstituting abilities after transplantation and show a surprisingly high proportion of actively cycling HSCs, suggesting that Gfi1 restrains proliferation of HSCs and thereby regulates their self‐renewal and long‐term engraftment abilities.