Almotiri, Alhomidi;
Boyd, Ashleigh S;
Rodrigues, Neil P;
(2023)
Zeb1 Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation.
Biomolecules
, 13
(9)
, Article 1386. 10.3390/biom13091386.
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Abstract
Zeb1, a zinc finger E-box binding homeobox epithelial–mesenchymal (EMT) transcription factor, acts as a critical regulator of hematopoietic stem cell (HSC) self-renewal and multi-lineage differentiation. Whether Zeb1 directly regulates the function of multi-potent progenitors primed for hematopoietic lineage commitment remains ill defined. By using an inducible Mx-1 Cre conditional mouse model where Zeb1 was genetically engineered to be deficient in the adult hematopoietic system (hereafter Zeb1⁻/⁻), we found that the absolute cell number of immunophenotypically defined lympho-myeloid primed progenitors (LMPPs) from Zeb1⁻/⁻ mice was reduced. Myeloid- and lymphoid-biased HSCs in Zeb1⁻/⁻ mice were unchanged, implying that defective LMPP generation from Zeb1⁻/⁻ mice was not directly caused by an imbalance of lineage-biased HSCs. Functional analysis of LMPP from Zeb1⁻/⁻ mice, as judged by competitive transplantation, revealed an overall reduction in engraftment to hematopoietic organs over 4 weeks, which correlated with minimal T-cell engraftment, reduced B-cell and monocyte/macrophage engraftment, and unperturbed granulocyte engraftment. Thus, Zeb1 regulates LMPP differentiation potential to select lympho-myeloid lineages in the context of transplantation.
Type: | Article |
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Title: | Zeb1 Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.3390/biom13091386 |
Publisher version: | https://doi.org/10.3390/biom13091386 |
Language: | English |
Additional information: | © The Author(s), 2023. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
Keywords: | Zeb1; hematopoiesis; differentiation |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10177287 |
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