AUTHOR=Yu Bo , Wu Bingyan , Hong Pingshan , Peng Huan , Zhang Mengyun , Zhang Qi , Liu Lijuan , Liu Xiaofei , Geng Yang , Wang Jinyong , Lan Yu 

TITLE=Co-Expression of Runx1, Hoxa9, Hlf, and Hoxa7 Confers Multi-Lineage Potential on Hematopoietic Progenitors Derived From Pluripotent Stem Cells

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.859769

DOI=10.3389/fcell.2022.859769

ISSN=2296-634X

ABSTRACT=<p>The intrinsic factors that determine the fundamental traits of engraftment ability and multi-lineage potential of hematopoietic stem cells (HSCs) remain elusive. The induction of bona fade HSCs from pluripotent stem cells (PSCs) in dishes is urgently demanded but remains a great challenge in translational medicine. <italic>Runx1</italic>, <italic>Hoxa9</italic>, <italic>Hlf</italic>, and <italic>Hoxa7</italic> are developmentally co-expressed during endothelial-to-hematopoietic transition and adult haematopoiesis. However, the expression of these factors fails to be turned on during <italic>in vitro</italic> hematopoietic induction from PSCs. Here, we established an inducible gene over-expression embryonic stem cell (ESC) line in which exogenous <italic>Runx1</italic>, <italic>Hoxa9</italic>, <italic>Hlf</italic>, and <italic>Hoxa7</italic> genes were tandemly knocked in. A population of induced hematopoietic progenitor cells (iHPCs) expressing Kit and Sca1 surface markers were successfully obtained <italic>in vitro</italic> from the gene edited-ESC line. Upon transplantation of the <italic>Runx1-Hoxa9-Hlf-Hoxa7</italic> ESC-derived iHPCs into irradiated immunodeficient mice, they can dominantly contribute to B cells, low proportions of T cells and myeloid cells. However, <italic>Runx1</italic>-<italic>Hoxa9</italic>-<italic>Hlf</italic> ESC-derived iHPCs only produced B lineage cells with extremely low contributions. Our study unveils that the coordination of <italic>Runx1</italic>, <italic>Hoxa9</italic>, <italic>Hlf</italic>, and <italic>Hoxa7</italic> led to generation of the hematopoietic progenitors with the capacity of multi-lineage hematopoietic reconstitution in the immunodeficient recipient mice.</p>