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Zeb1 Regulates the function of lympho-myeloid primed progenitors after transplantation

Almotiri, Alhomidi, Boyd, Ashleigh S. and Rodrigues, Neil P. ORCID: 2023. Zeb1 Regulates the function of lympho-myeloid primed progenitors after transplantation. Biomolecules 13 (9) , 1386. 10.3390/biom13091386

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: MDPI
ISSN: 2218-273X
Date of First Compliant Deposit: 11 September 2023
Date of Acceptance: 9 September 2023
Last Modified: 10 Oct 2023 08:49

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