Argonaute 2 Is Required for Extra-embryonic Endoderm Differentiation of Mouse Embryonic Stem Cells
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Date
2018-02-13
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Journal Article
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yes
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Abstract
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.
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Journal / series
Volume
10 (2)
Pages / Article No.
461 - 476
Publisher
Elsevier
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03983 - Ciaudo, C. (ehemalig) / Ciaudo, C. (former)
03983 - Ciaudo, C. (ehemalig) / Ciaudo, C. (former)
03983 - Ciaudo, C. (ehemalig) / Ciaudo, C. (former)
Notes
Funding
153220 - Nuclear role of the Argonaute proteins in mammalian embryonic stem cells (SNF)