Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells.
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.
Zeng
Hui
H
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Essen, Germany.
Yücel
Raif
R
Kosan
Christian
C
Klein-Hitpass
Ludger
L
Möröy
Tarik
T
D000483:Alleles; D000818:Animals; D016026:Bone Marrow Transplantation; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005434:Flow Cytometry; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D014184:Transplantation, Homologous
D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D014157:Transcription Factors