argonaute 2 is required for extra-embryonic endoderm differentiation of mouse embryonic stem cells

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ID: 157450
2018
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Ranked #26 of 101 articles by views in nature reviews gastroenterology & hepatology

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Abstract
Summary: In mouse, although four Argonaute (AGO) proteins with partly overlapping functions in small-RNA pathways exist, only Ago2 deficiency causes embryonic lethality. To investigate the role of AGO2 during mouse early development, we generated Ago2-deficient mouse embryonic stem cells (mESCs) and performed a detailed characterization of their differentiation potential. Ago2 disruption caused a global reduction of microRNAs, which resulted in the misregulation of only a limited number of transcripts. We demonstrated, both in vivo and in vitro, that AGO2 is dispensable for the embryonic germ-layer formation. However, Ago2-deficient mESCs showed a specific defect during conversion into extra-embryonic endoderm cells. We proved that this defect is cell autonomous and can be rescued by both a catalytically active and an inactive Ago2, but not by Ago2 deprived of its RNA binding capacity or by Ago1 overexpression. Overall, our results suggest a role for AGO2 in stem cell differentiation. : Ngondo et al. report that Ago2 is required for the extra-embryonic endoderm (ExEn) differentiation in vitro. While AGO2 is dispensable for proper embryo formation, its deletion in mESCs causes a decreased induction of ExEn genes, leading to an impaired differentiation. This defect is cell autonomous and involves AGO2 small-RNA binding capacity. Keywords: Argonaute 2, mouse embryonic stem cells, extra-embryonic endoderm, XEN cells, miRNA, differentiation, transcriptomics
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ngondo2018stemargonaute Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Richard Patryk Ngondo;Daniel Cirera-Salinas;Jian Yu;Harry Wischnewski;Maxime Bodak;Sandrine Vandormael-Pournin;Anna Geiselmann;Rahel Wettstein;Janina Luitz;Michel Cohen-Tannoudji;Constance Ciaudo
Journal nature reviews gastroenterology & hepatology
Year 2018
DOI
DOI not found
URL
http://www.sciencedirect.com/science/article/pii/S2213671117305714
Keywords
medicine (general)biology (general)

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