Person:
Badia-Careaga, Claudio

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Claudio
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Badia-Careaga
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CNIC
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2019 - 201922020 - 20221
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Author: Sainz de Aja, Julio ×

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    The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1
    (EMBO Press, 2019-04-01) 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; Ministerio de Ciencia, Innovación y Universidades (España); Wellcome Trust; Fundación ProCNIC
    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.
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    Nanog regulates Pou3f1 expression at the exit from pluripotency during gastrulation
    (The Company of Biologists, 2019-12) Barral, Antonio; Rollan, Isabel; Sanchez-Iranzo, Hector; Jawaid, Wajid; Badia-Careaga, Claudio; Menchero, Sergio; Gomez, Manuel J; Torroja, Carlos; Sanchez-Cabo, Fatima; Göttgens, Berthold; Manzanares, Miguel; Sainz de Aja, Julio; Ministerio de Ciencia, Innovación y Universidades (España); Wellcome Trust; Instituto de Salud Carlos III; Fundación ProCNIC
    Pluripotency is regulated by a network of transcription factors that maintain early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development is its expression restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses genes involved in anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog Use of Nanog null ES cells further demonstrated a role for Nanog in repressing a subset of anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting neural regulatory networks by repressing Pou3f1 at the onset of gastrulation.This article has an associated First Person interview with the joint first authors of the paper.
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    Pluripotency factors regulate the onset of Hox cluster activation in the early embryo.
    (American Association for the Advancement of Science (AAAS), 2022-07-15) Tiana, María; Lopez-Jimenez, Elena; Sainz de Aja, Julio; Barral, Antonio; Victorino, Jesus; Badia-Careaga, Claudio; Rollan, Isabel; Rouco, Raquel; Santos, Elisa; Sanchez-Iranzo, Hector; Acemel, Rafael D; Torroja, Carlos; Adan, Javier; Andrés-León, Eduardo; Gomez-Skarmeta, Jose Luis; Giovinazzo, Giovanna; Sanchez-Cabo, Fatima; Manzanares, Miguel; Ministerio de Ciencia e Innovación (España); Gobierno de Andalucía (España); Unión Europea. Comisión Europea. European Research Council (ERC); Fundación La Caixa; Ministerio de Ciencia e Innovación. Unidades de Excelencia María de Maeztu; Fundación Ramón Areces; Instituto de Salud Carlos III; Fundación ProCNIC; Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
    Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3' end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs.