<i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation
<i>Zeb1</i>, 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 <i>Zeb1</i> directly regulates the function of multi-pote...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/9/1386 |
| _version_ | 1797581100974866432 |
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| author | Alhomidi Almotiri Ashleigh S. Boyd Neil P. Rodrigues |
| author_facet | Alhomidi Almotiri Ashleigh S. Boyd Neil P. Rodrigues |
| author_sort | Alhomidi Almotiri |
| collection | DOAJ |
| description | <i>Zeb1</i>, 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 <i>Zeb1</i> directly regulates the function of multi-potent progenitors primed for hematopoietic lineage commitment remains ill defined. By using an inducible <i>Mx-1 Cre</i> conditional mouse model where <i>Zeb1</i> was genetically engineered to be deficient in the adult hematopoietic system (hereafter <i>Zeb1<sup>−/−</sup></i>), we found that the absolute cell number of immunophenotypically defined lympho-myeloid primed progenitors (LMPPs) from <i>Zeb1<sup>−/−</sup></i> mice was reduced. Myeloid- and lymphoid-biased HSCs in <i>Zeb1<sup>−/−</sup></i> mice were unchanged, implying that defective LMPP generation from <i>Zeb1<sup>−/−</sup></i> mice was not directly caused by an imbalance of lineage-biased HSCs. Functional analysis of LMPP from <i>Zeb1<sup>−/−</sup></i> 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, <i>Zeb1</i> regulates LMPP differentiation potential to select lympho-myeloid lineages in the context of transplantation. |
| first_indexed | 2024-03-10T22:59:26Z |
| format | Article |
| id | doaj.art-80be6a5c1cea43a4b1b0601076dd406e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T22:59:26Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-80be6a5c1cea43a4b1b0601076dd406e2023-11-19T09:46:16ZengMDPI AGBiomolecules2218-273X2023-09-01139138610.3390/biom13091386<i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after TransplantationAlhomidi Almotiri0Ashleigh S. Boyd1Neil P. Rodrigues2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Dawadmi, Shaqra University, Dawadmi 17464, Saudi ArabiaDepartment of Surgical Biotechnology, Division of Surgery and Interventional Science, Royal Free Hospital, University College London, London NW3 2PS, UKEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK<i>Zeb1</i>, 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 <i>Zeb1</i> directly regulates the function of multi-potent progenitors primed for hematopoietic lineage commitment remains ill defined. By using an inducible <i>Mx-1 Cre</i> conditional mouse model where <i>Zeb1</i> was genetically engineered to be deficient in the adult hematopoietic system (hereafter <i>Zeb1<sup>−/−</sup></i>), we found that the absolute cell number of immunophenotypically defined lympho-myeloid primed progenitors (LMPPs) from <i>Zeb1<sup>−/−</sup></i> mice was reduced. Myeloid- and lymphoid-biased HSCs in <i>Zeb1<sup>−/−</sup></i> mice were unchanged, implying that defective LMPP generation from <i>Zeb1<sup>−/−</sup></i> mice was not directly caused by an imbalance of lineage-biased HSCs. Functional analysis of LMPP from <i>Zeb1<sup>−/−</sup></i> 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, <i>Zeb1</i> regulates LMPP differentiation potential to select lympho-myeloid lineages in the context of transplantation.https://www.mdpi.com/2218-273X/13/9/1386<i>Zeb1</i>hematopoiesisdifferentiation |
| spellingShingle | Alhomidi Almotiri Ashleigh S. Boyd Neil P. Rodrigues <i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation Biomolecules <i>Zeb1</i> hematopoiesis differentiation |
| title | <i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation |
| title_full | <i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation |
| title_fullStr | <i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation |
| title_full_unstemmed | <i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation |
| title_short | <i>Zeb1</i> Regulates the Function of Lympho-Myeloid Primed Progenitors after Transplantation |
| title_sort | i zeb1 i regulates the function of lympho myeloid primed progenitors after transplantation |
| topic | <i>Zeb1</i> hematopoiesis differentiation |
| url | https://www.mdpi.com/2218-273X/13/9/1386 |
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