MYB bi-allelic targeting abrogates primitive clonogenic progenitors while the emergence of primitive blood cells is not affected.

Autor:	Shah Z; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Filonenko ES; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Ramensky V; Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia., Fan C; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Wang C; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Ullah H; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Zhang B; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China., Volchkov P; Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, Russia., Samokhvalov IM; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2021 Aug 01; Vol. 106 (8), pp. 2191-2202. Date of Electronic Publication: 2021 Aug 01.
DOI:	10.3324/haematol.2020.249193
Abstrakt:	MYB is a key regulator of definitive hematopoiesis and it is dispensable for the development of primitive hematopoietic cells in vertebrates. To delineate definitive versus primitive hematopoiesis during differentiation of human embryonic stem cells, we have introduced reporters into the MYB locus and inactivated the gene by bi-allelic targeting. To recapitulate the early developmental events more adequately, the mutant and wild type human embryonic stem cell lines were differentiated in defined culture conditions without the addition of hematopoietic cytokines. The differentiation of the reporter cell lines demonstrated that MYB is specifically expressed throughout emerging hematopoietic cell populations. Here we show that the disruption of the MYB gene leads to severe defects in the development and proliferation of primitive hematopoietic progenitors while the emergence of primitive blood cells is not affected. We also provide evidence that MYB is essential for neutrophil and T cell development and the upregulation of innate immunity genes during hematopoietic differentiation. Our results suggest that the endothelial origin of primitive blood cells is direct and does not include the intermediate step of primitive hematopoietic progenitors.
Databáze:	MEDLINE
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