Almotiri Alhomidi, Boyd Ashleigh S, Rodrigues Neil P
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences-Dawadmi, Shaqra University, Dawadmi 17464, Saudi Arabia.
European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building, Cardiff CF24 4HQ, UK.
Biomolecules. 2023 Sep 14;13(9):1386. doi: 10.3390/biom13091386.
, 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 directly regulates the function of multi-potent progenitors primed for hematopoietic lineage commitment remains ill defined. By using an inducible conditional mouse model where was genetically engineered to be deficient in the adult hematopoietic system (hereafter ), we found that the absolute cell number of immunophenotypically defined lympho-myeloid primed progenitors (LMPPs) from mice was reduced. Myeloid- and lymphoid-biased HSCs in mice were unchanged, implying that defective LMPP generation from mice was not directly caused by an imbalance of lineage-biased HSCs. Functional analysis of LMPP from 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, regulates LMPP differentiation potential to select lympho-myeloid lineages in the context of transplantation.
一种锌指E盒结合同源框上皮-间质(EMT)转录因子,作为造血干细胞(HSC)自我更新和多谱系分化的关键调节因子。它是否直接调节已准备好进行造血谱系定向的多能祖细胞的功能仍不清楚。通过使用一种诱导性条件小鼠模型,其中在成年造血系统中通过基因工程使其缺失(以下简称 ),我们发现来自 小鼠的免疫表型定义的淋巴-髓系定向祖细胞(LMPP)的绝对细胞数量减少。 小鼠中偏向髓系和淋巴系的造血干细胞没有变化,这意味着 小鼠中LMPP生成缺陷并非直接由偏向谱系的造血干细胞失衡引起。通过竞争性移植判断,对 小鼠的LMPP进行功能分析,结果显示在4周内移植到造血器官的细胞总体减少,这与极少的T细胞移植、减少的B细胞和单核细胞/巨噬细胞移植以及未受干扰的粒细胞移植相关。因此,在移植背景下, 调节LMPP分化潜能以选择淋巴-髓系谱系。