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PMID: 15385956 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells.

The EMBO journal ·Vol. 23 ·No. 20 ·2004-10-13 ·Pages 4116-25

Zeng H, Yücel R, Kosan C, Klein-Hitpass L, Möröy T

Abstract

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.

MeSH Terms
Alleles Animals Bone Marrow Transplantation Cell Cycle Cell Differentiation Cell Division Cell Lineage DNA-Binding Proteins/deficiency,genetics Flow Cytometry Gene Deletion Gene Expression Regulation, Developmental Hematopoiesis Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells/cytology,physiology Mice Mice, Knockout Models, Biological Reverse Transcriptase Polymerase Chain Reaction Transcription Factors/deficiency,genetics Transplantation, Homologous
Chemicals
DNA-Binding Proteins Gfi1 protein, mouse Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zeng Hui
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Essen, Germany.
Yücel Raif
Kosan Christian
Klein-Hitpass Ludger
Möröy Tarik
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600419
Published
2004-10-13
Epub
2004-00-23
Pages
4116-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC524350
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600419 PMC Full Text View journal details
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