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The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1
Author(s) -
Sainz de Aja Julio,
Menchero Sergio,
Rollan Isabel,
Barral Antonio,
Tiana Maria,
Jawaid Wajid,
Cossio Itziar,
Alvarez Alba,
CarreñoTarragona Gonzalo,
BadiaCareaga Claudio,
Nichols Jennifer,
Göttgens Berthold,
Isern Joan,
Manzanares Miguel
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899122
Subject(s) - homeobox protein nanog , biology , epiblast , nanog homeobox protein , embryonic stem cell , rex1 , microbiology and biotechnology , brachyury , stem cell , haematopoiesis , sox2 , induced pluripotent stem cell , genetics , embryo , embryogenesis , gastrulation , mesoderm , gene
Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from Brachyury ‐positive multipotent cells in the posterior‐proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite being expressed in the postimplantation epiblast. Using a dual transgene system for controlled expression at postimplantation stages, we found that Nanog blocks primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. Accordingly, Nanog ‐deficient embryonic stem cells are prone to erythropoietic differentiation. Moreover, Nanog expression in adults prevents the maturation of erythroid cells. By analysis of previous data for NANOG binding during stem cell differentiation and CRISPR /Cas9 genome editing, we found that Tal1 is a direct NANOG target. Our results show that Nanog regulates primitive hematopoiesis by directly repressing critical erythroid lineage specifiers.