Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate

• DOI: 10.3389/fcell.2021.728057
• Publication Date: 2021-09-13T05:11:06Z
• Authors: Wanbo Tang; Jian He; Tao Huang; Zhijie Bai; Chaojie Wang; Haizhen Wang; Ruichuang Yang; Yanli Ni; Jun Hou; Junliang Wang; Jie Zhou; Yingpeng Yao; Yandong Gong; Siyuan Hou; Bing Liu; Yu Lan
• Keywords: Hematopoietic stem cell

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic (HSCs). As HECs also generate a lot progenitors not fated to HSCs, powerful tools that pre-HSC/HSC-specific become urgently critical. Here, using gene knockin strategy, we firstly developed an Hlf-tdTomato reporter model detected expression exclusively in including part immunophenotypic CD45 – + pre-HSCs embryonic day (E) 10.5 AGM region. By vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, further revealed unlike counterpart which both Hlf-tdTomato-positive negative sub-populations harbored competence, E10.5 existed cells. The result indicates should gain Hlf prior or give rise functional HSCs. Furthermore, constructed novel Hlf-CreER performed time-restricted genetic lineage tracing single dose induction at E9.5. We observed labeling E11.5 precursors their contribution HSCs fetal liver (FL). Importantly, these Hlf-labeled early contributed retained size pool bone marrow (BM), continuously differentiated maintain balanced multi-lineage hematopoiesis adult. Therefore, provided another valuable specifically trace fate emerging during development.