Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells
Top Cited Papers
Open Access
- 23 September 2004
- journal article
- Published by Springer Nature in The EMBO Journal
- Vol. 23 (20) , 4116-4125
- https://doi.org/10.1038/sj.emboj.7600419
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.Keywords
This publication has 56 references indexed in Scilit:
- Gfi1:Green Fluorescent Protein Knock-in Mutant Reveals Differential Expression and Autoregulation of the Growth Factor Independence 1 (Gfi1) Gene during Lymphocyte DevelopmentJournal of Biological Chemistry, 2004
- The Transcriptional Repressor Gfi1 Affects Development of Early, Uncommitted c-Kit+ T Cell Progenitors and CD4/CD8 Lineage Decision in the ThymusThe Journal of Experimental Medicine, 2003
- The zinc finger transcription factorGfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survivalDevelopment, 2003
- Overexpression of a dominant negative form of STAT3 selectively impairs hematopoietic stem cell activityOncogene, 2002
- Growth Factor Independent-1 Induced by IL-4 Regulates Th2 Cell ProliferationPublished by Elsevier ,2002
- Inflammatory reactions and severe neutropenia in mice lacking the transcriptional repressor Gfi1Nature Genetics, 2002
- Upregulation of Flt3 Expression within the Bone Marrow Lin−Sca1+c-kit+ Stem Cell Compartment Is Accompanied by Loss of Self-Renewal CapacityImmunity, 2001
- Stem CellsCell, 2000
- Zinc finger protein GFI-1 has low oncogenic potential but cooperates strongly with pim and myc genes in T-cell lymphomagenesisOncogene, 1998
- The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotypeImmunity, 1994