Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-10

AUTHORS

Hanno Hock, Melanie J. Hamblen, Heather M. Rooke, Jeffrey W. Schindler, Shireen Saleque, Yuko Fujiwara, Stuart H. Orkin

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. More... »

PAGES

1002

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature02994

DOI

http://dx.doi.org/10.1038/nature02994

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044077721

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15457180


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