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Zeb1 Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation

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. Green open access

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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
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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