Charles-�tienne Lebert-Ghali
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
Marilaine Fournier
Laura M.J. Kettyle
ALEXANDER THOMPSON Alex.Thompson@nottingham.ac.uk
Associate Professor
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.-É., 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 | Nov 9, 2016 |
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. |
Contract Date | Nov 9, 2016 |
Files
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