The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

• Julio Sainz de Aja ^[1] ; Sergio Menchero ^[1] ; Isabel Rollan ^[1] ; Antonio Barral ^[1] ; Maria Tiana ^[1] ; Wajid Jawaid ^[3] ; Itziar Cossio ^[1] ; Alba Alvarez ^[1] ; Gonzalo Carreño‐Tarragona ^[4] ; Claudio Badia‐Careaga ^[1] ; Jennifer Nichols ^[2] ; Berthold Göttgens ^[3] ; Joan Isern ^[1] ; Miguel Manzanares ^[1]
  1. [1] Centro Nacional de Investigaciones Cardiovasculares Carlos III

     Centro Nacional de Investigaciones Cardiovasculares Carlos III

     Madrid, España

     
  2. [2] Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute

     Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute

     Cambridge District, Reino Unido

     
  3. [3] 2 Wellcome‐Medical Research Council Cambridge Stem Cell Institute Cambridge UK; 3 Department of Haematology Cambridge Institute for Medical Research University of Cambridge Cambridge UK
  4. [4] 1 Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) Madrid Spain; 4 Department of Haematology Hospital 12 de Octubre Madrid Spain

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 7, 2019
• Idioma: inglés
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  • 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.