|
|
Blood, 15 January 2006, Vol. 107, No. 2, pp. 492-500.
Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-02-0529.
 Previous Article | Next Article 
Submitted February 8, 2005
Accepted July 20, 2005
Expression of Pitx2 in stromal cells is required for normal hematopoiesis
Aurelie Kieusseian, Jalila Chagraoui, Cecile Kerdudo, Philippe-Emmanuel Mangeot, Philip J Gage, Nicole Navarro, Brigitte Izac, Georges Uzan, Bernard G Forget, and Anne Dubart-Kupperschmitt*
Institut Cochin, Departement d'Hematologie, INSERM U567, CNRS UMR 8104, Universite Paris Descartes, Faculte de Medecine Rene Descartes, Paris, France
U506 INSERM, Hopital Paul Brousse, Villejuif, France
Human Genetics, Michigan University, Ann Arbor, MI, USA
Medicine/Genetics, Yale University School of Medicine, New Haven, CT, USA
* Corresponding author; email: dubart{at}cochin.inserm.fr.
Although the expression of Pitx2, a bicoid family homeodomain transcription factor, is highly regulated during hematopoiesis, its function during this process is not documented. To elucidate this function, we studied hematopoiesis in Pitx2 null mice. We found that Pitx2 -/- embryos display hypoplastic livers with reduced numbers of hematopoietic cells, but the hematopoietic CD45+ cells from Pitx2 -/- fetal livers had normal hematopoietic potential, as evidenced by colony forming assays, immature progenitor cell assays and long-term repopulation assays. Because the microenvironment is also crucial to the development of normal hematopoiesis, we established Pitx2-/- and Pitx2+/+ stromal cells from fetal liver and studied their hematopoietic supportive capacity. We showed that the frequency of cobblestone area forming cells (CAFC) was 4 fold decreased when using Pitx2-/- stromal cells compared to Pitx2 +/+ stromal cells, whatever the Pitx2 genotype of hematopoietic CD45+ cells tested in this assay. This defect was rescued by lentiviral transduction of the Pitx2 coding sequence into Pitx2-/- fetal liver stromal cells, demonstrating a major and direct role of Pitx2 in the hematopoietic supportive capacity of fetal liver stroma. Finally, we showed a reduced capacity of the MS5 stromal cell line to support human hematopoiesis after transduction with a Pitx2 RNAi expressing vector. Taken together, these data showed that Pitx2 has major functions in the hematopoietic supportive capacity of fetal liver and adult bone marrow stromal cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Xu, S. Eleswarapu, H. Geiger, K. Szczur, D. Daria, Y. Zheng, J. Settleman, E. F. Srour, D. A. Williams, and M.-D. Filippi
Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential
Blood,
October 22, 2009;
114(17):
3557 - 3566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lagergren, R. Mansson, J. Zetterblad, E. Smith, B. Basta, D. Bryder, P. Akerblad, and M. Sigvardsson
The Cxcl12, Periostin, and Ccl9 Genes Are Direct Targets for Early B-cell Factor in OP-9 Stroma Cells
J. Biol. Chem.,
May 11, 2007;
282(19):
14454 - 14462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Keller, S. Addya, R. Vadigepalli, B. Banini, K. Delgrosso, H. Huang, and S. Surrey
Transcriptional regulatory network analysis of developing human erythroid progenitors reveals patterns of coregulation and potential transcriptional regulators
Physiol Genomics,
December 13, 2006;
28(1):
114 - 128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
