Advanced

HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development.

Magnusson, Mattias LU ; Brun, Ann LU ; Miyake, Noriko LU ; Larsson, Jonas LU ; Ehinger, Mats LU ; Björnsson, Jon Mar LU ; Wutz, Anton; Sigvardsson, Mikael LU and Karlsson, Stefan LU (2007) In Blood 109(9). p.3687-3696
Abstract
The Homeobox (Hox) transcription factors are important regulators of normal and malignant hematopoiesis because they control proliferation, differentiation, and self-renewal of hematopoietic cells at different levels of the hematopoietic hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13 days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10 was dependent on the HOXA10 concentration, because high levels of HOXA10 had no effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid and megakaryocyte... (More)
The Homeobox (Hox) transcription factors are important regulators of normal and malignant hematopoiesis because they control proliferation, differentiation, and self-renewal of hematopoietic cells at different levels of the hematopoietic hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13 days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10 was dependent on the HOXA10 concentration, because high levels of HOXA10 had no effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid and megakaryocyte development, demonstrating that tight regulation of HOXA10 is critical for normal development of the erythroid and megakaryocytic lineages. The HOXA10-mediated effects on hematopoietic cells were associated with altered expression of genes that govern stem-cell self-renewal and lineage commitment (eg, hepatic leukemia factor [HlF], Dickkopf-1 [Dkk-1], growth factor independent-1 [Cfl-1], and Gata-1). Interestingly, binding sites for HOXA10 were found in HLF, Dkk-1, and Gata-1, and Dkk-1 and Gfl-1 were transcriptionally activated by HOXA10. These findings reveal novel molecular pathways that act downstream of HOXA10 and identify HOXA10 as a master regulator of postnatal hematopoietic development. (C) 2007 by The American Society of Hematology. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
109
issue
9
pages
3687 - 3696
publisher
American Society of Hematology
external identifiers
  • wos:000246091400021
  • scopus:34247378195
ISSN
1528-0020
DOI
10.1182/blood-2006-10-054676
language
English
LU publication?
yes
id
c23719d0-b6d9-4224-abd4-4c42c72b4d2f (old id 164777)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17234739&dopt=Abstract
date added to LUP
2007-07-11 12:41:43
date last changed
2017-10-22 03:51:26
@article{c23719d0-b6d9-4224-abd4-4c42c72b4d2f,
  abstract     = {The Homeobox (Hox) transcription factors are important regulators of normal and malignant hematopoiesis because they control proliferation, differentiation, and self-renewal of hematopoietic cells at different levels of the hematopoietic hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13 days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10 was dependent on the HOXA10 concentration, because high levels of HOXA10 had no effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid and megakaryocyte development, demonstrating that tight regulation of HOXA10 is critical for normal development of the erythroid and megakaryocytic lineages. The HOXA10-mediated effects on hematopoietic cells were associated with altered expression of genes that govern stem-cell self-renewal and lineage commitment (eg, hepatic leukemia factor [HlF], Dickkopf-1 [Dkk-1], growth factor independent-1 [Cfl-1], and Gata-1). Interestingly, binding sites for HOXA10 were found in HLF, Dkk-1, and Gata-1, and Dkk-1 and Gfl-1 were transcriptionally activated by HOXA10. These findings reveal novel molecular pathways that act downstream of HOXA10 and identify HOXA10 as a master regulator of postnatal hematopoietic development. (C) 2007 by The American Society of Hematology.},
  author       = {Magnusson, Mattias and Brun, Ann and Miyake, Noriko and Larsson, Jonas and Ehinger, Mats and Björnsson, Jon Mar and Wutz, Anton and Sigvardsson, Mikael and Karlsson, Stefan},
  issn         = {1528-0020},
  language     = {eng},
  number       = {9},
  pages        = {3687--3696},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development.},
  url          = {http://dx.doi.org/10.1182/blood-2006-10-054676},
  volume       = {109},
  year         = {2007},
}