Journal
STEM CELL REPORTS
Volume 9, Issue 5, Pages 1588-1603Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.10.011
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Funding
- Braukmann-Wittenberg-Herz-Stiftung
- Deutsche Forschungsgemeinschaft
- German Ministry for Education and Research, IFB-Tx
- REBIRTH Excellence Cluster
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Pluripotent stem cells hold great promise for regenerative medicine since they can differentiate into all somatic cells. MicroRNAs (miRNAs) could be important for the regulation of these cell-fate decisions. Profiling of miRNAs revealed 19 differentially expressed miRNAs in the endoderm and 29 in the mesoderm when analyzing FACS-purified cells derived from human embryonic stem cells. The mesodermal-enriched miR-483-3p was identified as an important regulator for the generation of mesodermal PDGFRA(+) paraxial cells. Repression of its target PGAM1 significantly increased the number of PDGFRA(+) cells. Furthermore, miR-483-3p, miR-199a-3p, and miR-214-3p might also have functions for the mesodermal progenitors. The endoderm-specific miR-489-3p and miR-1263 accelerated and increased endoderm differentiation upon overexpression. KLF4 was identified as a target of miR-1263. RNAi-mediated downregulation of KLF4 partially mimicked miR-1263 overexpression. Thus, the effects of this miRNA were mediated by facilitating differentiation through destabilization of pluripotency along with other not yet defined targets.
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