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2022_iScience_Fine_MontserratN.pdf (7.72 MB)

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2022-07-15

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cc by-nc-nd (c) Astro, Veronica et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/188730

Fine-tuned KDM1A alternative splicing regulates human cardiomyogenesis through an enzymatic-independent mechanism

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Recurs relacionat

https://doi.org/10.1016/j.isci.2022.104665

Resum

The histone demethylase KDM1A is a multi- faceted regulator of vital developmental processes, including mesodermal and cardiac tube formation during gastrulation. However, it is unknown whether the fine-tuning of KDM1A splicing isoforms, already shown to regulate neuronal maturation, is crucial for the specification and maintenance of cell identity during cardiogenesis. Here, we discovered a temporal modulation of ubKDM1A and KDM1A+2a during human and mice fetal cardiac development and evaluated their impact on the regulation of cardiac differentiation. We revealed a severely impaired cardiac differentiation in KDM1A(-/-) hESCs that can be rescued by re-expressing ubKDM1A or catalytically impaired ubKDM1A-K661A, but not by KDM1A+2a or KDM1A+2a-K661A. Conversely, KDM1A+2a(-/-) hESCs give rise to functional cardiac cells, displaying increased beating amplitude and frequency and enhanced expression of critical cardiogenic markers. Our findings prove the existence of a divergent scaffolding role of KDM1A splice variants, independent of their enzymatic activity, during hESC differentiation into cardiac cells.

Matèries

Cèl·lules mare, Regulació genètica, Cèl·lules

Matèries (anglès)

Stem cells, Genetic regulation, Cells

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Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

Citació

ASTRO, Veronica, RAMIREZ CALDERON, Gustavo, PENNUCCI, Roberta, CAROLI, Jonatan, SAERA VILA, Alfonso, CARDONA LONDOÑO, Kelly, FORASTIERI, Chiara, FIACCO, Elisabetta, MAKSOUD, Fatima, ALOWAYSI, Maryam, SOGNE, Elisa, FALQUI, Andrea, GONZÁLEZ, Federico, MONTSERRAT, Nuria, BATTAGLIOLI, Elena, MATTEVI, Andrea, ADAMO, Antonio. Fine-tuned KDM1A alternative splicing regulates human cardiomyogenesis through an enzymatic-independent mechanism. _Iscience_. 2022. Vol. 25, núm. 7, pàgs. 104665. [consulta: 27 de gener de 2026]. ISSN: 2589-0042. [Disponible a: https://hdl.handle.net/2445/188730]

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