Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells
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−/−) result...
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American Society of Hematology
2016
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| Online Access: | https://eprints.nottingham.ac.uk/38605/ |
| _version_ | 1848795650499543040 |
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| author | Lebert-Ghali, Charles-Étienne Fournier, Marilaine Kettyle, Laura M.J. Thompson, Alexander Sauvageau, Guy Bijl, Janet J. |
| author_facet | Lebert-Ghali, Charles-Étienne Fournier, Marilaine Kettyle, Laura M.J. Thompson, Alexander Sauvageau, Guy Bijl, Janet J. |
| author_sort | Lebert-Ghali, Charles-Étienne |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:35:28Z |
| format | Article |
| id | nottingham-38605 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:35:28Z |
| publishDate | 2016 |
| publisher | American Society of Hematology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-386052020-05-04T17:33:05Z https://eprints.nottingham.ac.uk/38605/ Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells Lebert-Ghali, Charles-Étienne Fournier, Marilaine Kettyle, Laura M.J. Thompson, Alexander Sauvageau, Guy Bijl, Janet J. 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. American Society of Hematology 2016-01-07 Article PeerReviewed Lebert-Ghali, Charles-Étienne, Fournier, Marilaine, Kettyle, Laura M.J., Thompson, Alexander, Sauvageau, Guy and Bijl, Janet J. (2016) Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells. Blood, 127 (1). pp. 87-90. ISSN 1528-0020 http://dx.doi.org/10.1182/blood-2015-02-626390 doi:10.1182/blood-2015-02-626390 doi:10.1182/blood-2015-02-626390 |
| spellingShingle | Lebert-Ghali, Charles-Étienne Fournier, Marilaine Kettyle, Laura M.J. Thompson, Alexander Sauvageau, Guy Bijl, Janet J. Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| title | Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| title_full | Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| title_fullStr | Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| title_full_unstemmed | Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| title_short | Hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| title_sort | hoxa cluster genes determine the proliferative activity of adult mouse hematopoietic stem and progenitor cells |
| url | https://eprints.nottingham.ac.uk/38605/ https://eprints.nottingham.ac.uk/38605/ https://eprints.nottingham.ac.uk/38605/ |