Argonaute 2 Is Required for Extra-embryonic Endoderm Differentiation of Mouse Embryonic Stem Cells

Richard Patryk Ngondo (1) , Daniel Cirera-Salinas (1) , Jian Yu (1, 2) , Harry Wischnewski (1) , Maxime Bodak (1, 2) , Sandrine Vandormael-Pournin (3) , Anna Geiselmann (3) , Rahel Wettstein (1, 2) , Janina Luitz (1) , Michel Cohen-Tannoudji (3) , Constance C. Ciaudo (1)

1 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
2 UZH - Universität Zürich [Zürich] = University of Zurich
3 Génétique fonctionnelle de la Souris

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.

Keywords: Argonaute 2; XEN cells; differentiation; extra-embryonic endoderm; miRNA; mouse embryonic stem cells; transcriptomics

Domains: Life Sciences [q-bio]; Development Biology

Richard Patryk Ngondo, Daniel Cirera-Salinas, Jian Yu, Harry Wischnewski, Maxime Bodak, et al.. Argonaute 2 Is Required for Extra-embryonic Endoderm Differentiation of Mouse Embryonic Stem Cells. Stem Cell Reports, 2018, 10 (2), pp.461-476. ⟨10.1016/j.stemcr.2017.12.023⟩. ⟨pasteur-02075458⟩