Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells
by
Laetitia Barrault 1, Jacqueline Gide 1, Tingting Qing 1, Lea Lesueur 2, Jorg Tost 3
, Jerome Alexandre Denis 2, Michel Cailleret 2, Laetitia Aubry 2, Marc Peschanski 1,2, Cécile Martinat 2,* and Sandrine Baghdoyan 2
Laetitia Barrault 1, Jacqueline Gide 1, Tingting Qing 1, Lea Lesueur 2, Jorg Tost 3, Jerome Alexandre Denis 2, Michel Cailleret 2, Laetitia Aubry 2, Marc Peschanski 1,2, Cécile Martinat 2,* and Sandrine Baghdoyan 2
1
CECS/AFM, I-STEM, 91100 Corbeil-Essonnes, France
2
INSERM/ UEVE UMR 861, Paris Saclay Univ I-STEM, 91100 Corbeil-Essonnes, France
3
LEE/ CNRGH/ CEA—IBFJ 2, 91000 Evry, France
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1523; https://doi.org/10.3390/cells8121523
Received: 27 August 2019 / Revised: 8 November 2019 / Accepted: 19 November 2019 / Published: 26 November 2019
(This article belongs to the Section Stem Cells)
Substantial variations in differentiation properties have been reported among human pluripotent cell lines (hPSC), which could affect their utility and clinical safety. We characterized the variable osteogenic capacity observed between different human pluripotent stem cell lines. By focusing on the miRNA expression profile, we demonstrated that the osteogenic differentiation propensity of human pluripotent stem cell lines could be associated with the methylation status and the expression of miRNAs from the imprinted DLK1/DIO3 locus. More specifically, quantitative analysis of the expression of six different miRNAs of that locus prospectively identified human embryonic stem cells and human-induced pluripotent stem cells with differential osteogenic differentiation capacities. At the molecular and functional levels, we showed that these miRNAs modulated the expression of the activin receptor type 2B and the downstream signal transduction, which impacted osteogenesis. In conclusion, miRNAs of the imprinted DLK1/DIO3 locus appear to have both a predictive value and a functional impact in determining the osteogenic fate of human pluripotent stem cells.
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Keywords:
human pluripotent stem cells; microRNA; imprinting; osteogenic differentiation; variability; ACVR2B
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Barrault, L.; Gide, J.; Qing, T.; Lesueur, L.; Tost, J.; Denis, J.A.; Cailleret, M.; Aubry, L.; Peschanski, M.; Martinat, C.; Baghdoyan, S. Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells. Cells 2019, 8, 1523.
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