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A critical pathway in human development: C19MC micrornas regulates FGF2 response in a model of human pluripotent stem cells cardiac differentiation

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dc.contributor.author Möbbs, Alan Miqueas
dc.contributor.author Garate, Ximena
dc.contributor.author Scarafia, María Agustina
dc.contributor.author Colli, Carolina
dc.contributor.author Moro, Lucía Natalia
dc.contributor.author Luzzani, Carlos Daniel
dc.contributor.author Waisman, Ariel
dc.contributor.author La Greca, Alejandro
dc.contributor.author Miriuka, Santiago Gabriel
dc.date.accessioned 2023-02-22T14:50:58Z
dc.date.available 2023-02-22T14:50:58Z
dc.date.issued 2021-11
dc.identifier.citation Alan Miqueas Möbbs, Ximena Garate, Maria Agustina Scarafia, Carolina Colli, Natalia Lucía Moro, Carlos Daniel Luzzani, Ariel Waisman, Alejandro La Greca, Santiago Gabriel Miriuka. A critical pathway in human development: C19MC micrornas regulates FGF2 response in a model of human pluripotent stem cells cardiac differentiation. Annual Meeting of Bioscience Societies November 17-20 2021. MEedicina (Buenos Aires) 2021; 81 (Supl. III) es_ES
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/788
dc.description.abstract Human pluripotent stem cells (hPSC) have the capacity to self-renew and differentiate in vitro into all cell types of the organism, and it is an established model for early human embryo development. Recently, we found a 56-miRNA- cluster located at human chromosome 19 (C19MC) that downregulates during hPSC cardiac differentiation (CD). To ascertain the role of this primate-specific microRNA cluster, a hPSC-C19MC(-/-) line was generated with CRISPR/Cas9. C19MC(-/-) cells displayed no evident changes in the cell cycle, apoptosis or differentiation markers compared to wild type. Contrarily, C19MC(-/-) cells were significantly impaired to differentiate into cardiomyocytes. Early mesoderm and cardiac RNA markers, like EOMES, TBX6, MESP1, were found altered. In order to further explore the early steps of differentiation, we performed RNA-seq of the cells at the gastrulation stage (0 and 24hs after CHIR99021 incubation). Gene ontology analysis revealed altered signaling pathways, including PI3K-Akt, MAPK and Wnt, and FGF2. As FGF2 is a key pathway in pluripotency, we address its role through two different approaches. First, both wild type and mutant cells were treated with FGF2 for 3 hours before gastrulation. Wild-type phenotype was partly recovered, as evidenced by the presence of contractile cardiomyocytes at day 15. Second, given that FGF2 is an important activator of RAS cascade that phosphorylates ERK1/2 (pERK), we incubated the cells with FGF2 for up to 5 hs in pluripotency media. Mutant cells exhibited an elevated pERK mark in ground conditions, and it was noticeable that the phosphorylation took place faster when they were treated. In summary these findings support a critical role of the C19MC microRNA cluster in early stages of primate differentiation. es_ES
dc.language.iso eng es_ES
dc.publisher Fundación Revista Medicina es_ES
dc.title A critical pathway in human development: C19MC micrornas regulates FGF2 response in a model of human pluripotent stem cells cardiac differentiation es_ES
dc.type Presentation es_ES
dc.type.snrd Presentation es_ES


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