Almotiri, Alhomidi, Boyd, Ashleigh S. and Rodrigues, Neil P.  ORCID: https://orcid.org/0000-0002-1925-7733
2023.
Zeb1 Regulates the function of lympho-myeloid primed progenitors after transplantation.
Biomolecules
13
(9)
, 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.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Biosciences Research Institutes & Centres > 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 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/162382 |
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