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

First Author  Almotiri A Year  2023
Journal  Biomolecules Volume  13
Issue  9 PubMed ID  37759786
Mgi Jnum  J:342508 Mgi Id  MGI:7537511
Doi  10.3390/biom13091386 Citation  Almotiri A, et al. (2023) Zeb1 Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation. Biomolecules 13(9)
abstractText  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.
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