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

The EMBO Journal
Hui ZengTarik Möröy

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.

References

Jul 1, 1988·Science·G J SpangrudeI L Weissman
Aug 1, 1996·Molecular and Cellular Biology·P A Zweidler-MckayP N Tsichlis
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·S KimuraW S Alexander
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·S H CheshierI L Weissman
Nov 2, 1999·The Journal of Experimental Medicine·A NichogiannopoulouK Georgopoulos
Mar 10, 2000·Science·T ChengD T Scadden
Nov 9, 2000·The Journal of Experimental Medicine·F N KaranuM Bhatia
Mar 10, 2001·Methods in Molecular Biology·I Bertoncello, B Williams
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·J L Christensen, I L Weissman
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Jeffrey M Trimarchi, Jacqueline A Lees
Apr 30, 2003·Nature·Tannishtha ReyaIrving L Weissman
May 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhijun Duan, Marshall Horwitz
May 16, 2003·Molecular and Cellular Biology·Jon Mar BjörnssonStefan Karlsson
Jun 5, 2003·The Journal of Experimental Medicine·Jean-Francois LambertPeter J Quesenberry

❮ Previous
Next ❯

Citations

Sep 24, 2010·Leukemia·L T van der MeerB A van der Reijden
Oct 22, 2013·Nature Immunology·Chauncey J SpoonerHarinder Singh
Jan 30, 2007·Nature Reviews. Immunology·Frank Rosenbauer, Daniel G Tenen
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Suchitra BasuFan Dong
May 8, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jerome DicksteinGiuseppina Nucifora
Jan 2, 2007·The Journal of Biological Chemistry·Richard DahlM Celeste Simon
Aug 15, 2008·The Journal of Biological Chemistry·Ryo ShinnakasuToshinori Nakayama
Aug 30, 2008·The Journal of Experimental Medicine·Zhijian QianMichelle M Le Beau
Dec 28, 2011·The Journal of Experimental Medicine·Danae SchulzMark S Schlissel
Jul 25, 2007·Bioinformatics·Jeroen de RidderMarcel Reinders
Jun 24, 2010·Current Opinion in Hematology·James D PhelanH Leighton Grimes
Feb 18, 2011·Genes & Development·Scott A Lacadie, Leonard I Zon
Jul 20, 2007·Molecular and Cellular Biology·Zhijun DuanMarshall S Horwitz
Oct 4, 2006·The Journal of Clinical Investigation·Michelle B BowieConnie J Eaves
Feb 23, 2008·The Journal of Clinical Investigation·Fulu LiuDaniel C Link
Oct 21, 2006·Blood·Marshall S HorwitzStephen J Salipante
Jul 25, 2007·Blood·Jurgen A F MarteijnBert A Van der Reijden
Apr 7, 2009·Blood·Shane R HormanH Leighton Grimes
Mar 13, 2009·Blood·Chinavenmeni S VeluH Leighton Grimes
Feb 25, 2011·Stem Cell Research & Therapy·Nicola K WilsonBerthold Göttgens

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.