The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

Sainz de Aja, Julio; Menchero, Sergio; Rollan, Isabel; Barral, Antonio; Tiana, Maria; Jawaid, Wajid; Cossio, Itziar; Alvarez, Alba; Carreño-Tarragona, Gonzalo; Badia-Careaga, Claudio; Nichols, Jennifer; Göttgens, Berthold; Isern, Joan; Manzanares, Miguel

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1

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dc.contributor.author Sainz de Aja, Julio
dc.contributor.author Menchero, Sergio
dc.contributor.author Rollan, Isabel
dc.contributor.author Barral, Antonio
dc.contributor.author Tiana, Maria
dc.contributor.author Jawaid, Wajid
dc.contributor.author Cossio, Itziar
dc.contributor.author Alvarez, Alba
dc.contributor.author Carreño-Tarragona, Gonzalo
dc.contributor.author Badia-Careaga, Claudio
dc.contributor.author Nichols, Jennifer
dc.contributor.author Göttgens, Berthold
dc.contributor.author Isern, Joan
dc.contributor.author Manzanares, Miguel
dc.date.accessioned 2023-02-06T07:23:05Z
dc.date.available 2023-02-06T07:23:05Z
dc.date.issued 2019
dc.description Includes supplementary materials: online appendix; replication data
dc.description.abstract 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.
dc.description.sponsorship This work was supported by the Spanish government (grant BFU2014-54608-P and BFU2017-84914-P to MM; grants RYC-2011-09209 and BFU-2012-35892 to JI). The Gottgens and Nichols laboratories are supported by core funding from the Wellcome Trust and MRC to the Wellcome and MRC Cambridge Stem Cell Institute. The CNIC is supported by the Spanish Ministry of Science, Innovation and Universities (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).
dc.format.mimetype application/pdf
dc.identifier.citation Sainz J, Menchero S, Rollan I, Barral A, Tian M, Jawaid W, et al. The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1. The EMBO Journal. 2019 Apr 01;38(7):e99122. DOI: 10.15252/embj.201899122
dc.identifier.doi http://dx.doi.org/10.15252/embj.201899122
dc.identifier.issn 0261-4189
dc.identifier.uri http://hdl.handle.net/10230/55614
dc.language.iso eng
dc.publisher EMBO Press
dc.relation.ispartof The EMBO Journal. 2019 Apr 01;38(7):e99122
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SEV2015-0505
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54608-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-84914-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-35892
dc.rights This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Erythropoiesis
dc.subject.keyword Gastrulation
dc.subject.keyword Nanog
dc.subject.keyword Primitive hematopoiesis
dc.subject.keyword Tal1
dc.title The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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