Skip to main content

Research Repository

Advanced Search

Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells

Lebert-Ghali, Charles-�tienne; Fournier, Marilaine; Kettyle, Laura M.J.; Thompson, Alexander; Sauvageau, Guy; Bijl, Janet J.

Authors

Charles-�tienne Lebert-Ghali

Marilaine Fournier

Laura M.J. Kettyle

Guy Sauvageau

Janet J. Bijl



Abstract

Determination of defined roles for endogenous homeobox (Hox) genes in adult hematopoietic stem and progenitor cell (HSPC) activity has been hampered by a combination of embryonic defects and functional redundancy. Here we show that conditional homozygous deletion of the Hoxa cluster (Hoxa−/−) results in a marked reduction of adult HSPC activity, both in vitro and in vivo. Specifically, proliferation of Hoxa−/− HSPCs is reduced compared with wild-type (WT) cells in vitro and they are less competitive in vivo. Notably, the loss of Hoxa genes had little impact on HSPC differentiation. Comparative RNA sequencing analyses of Hoxa−/− and WT hematopoietic stem cells (CD150+/CD48−/Lineage−/c-kit+/Sca-1+) identified a large number of differentially expressed genes, three of which (Nr4a3, Col1a1, and Hnf4a) showed >10-fold reduced levels. Engineered overexpression of Hoxa9 in Hoxa−/− HSPCs resulted in partial phenotypic rescue in vivo with associated recovery in expression of a large proportion of deregulated genes. Together, these results provide definitive evidence linking Hoxa gene expression to proliferation of adult HSPCs.

Citation

Lebert-Ghali, C., Fournier, M., Kettyle, L. M., Thompson, A., Sauvageau, G., & Bijl, J. J. (2016). Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells. Blood, 127(1), 87-90. https://doi.org/10.1182/blood-2015-02-626390

Journal Article Type Article
Acceptance Date Oct 26, 2015
Online Publication Date Nov 19, 2015
Publication Date Jan 7, 2016
Deposit Date Nov 9, 2016
Publicly Available Date Mar 29, 2024
Journal Blood
Print ISSN 0006-4971
Electronic ISSN 1528-0020
Publisher American Society of Hematology
Peer Reviewed Peer Reviewed
Volume 127
Issue 1
Pages 87-90
DOI https://doi.org/10.1182/blood-2015-02-626390
Public URL https://nottingham-repository.worktribe.com/output/773403
Publisher URL http://dx.doi.org/10.1182/blood-2015-02-626390
Additional Information This research was originally published in Blood. Charles-Étienne Lebert-Ghali, Marilaine Fournier, Laura Kettyle, Alexander Thompson, Guy Sauvageau and Janet J. Bijl
Blood 2016 127: pp. 87-90; doi:10.1182/blood-2015-02-626390 © the American Society of Hematology.

Files





You might also like



Downloadable Citations