The PIDDosome controls cardiomyocyte polyploidization during postnatal heart development
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| Publicado en: | bioRxiv (Feb 19, 2025) |
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| Autor principal: | |
| Otros Autores: | , , , , , , , , , , , , , , , |
| Publicado: |
Cold Spring Harbor Laboratory Press
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| Materias: | |
| Acceso en línea: | Citation/Abstract Full Text - PDF Full text outside of ProQuest |
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| 001 | 3168488963 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2692-8205 | ||
| 024 | 7 | |a 10.1101/2024.08.27.609375 |2 doi | |
| 035 | |a 3168488963 | ||
| 045 | 0 | |b d20250219 | |
| 100 | 1 | |a Leone, Marina | |
| 245 | 1 | |a The PIDDosome controls cardiomyocyte polyploidization during postnatal heart development | |
| 260 | |b Cold Spring Harbor Laboratory Press |c Feb 19, 2025 | ||
| 513 | |a Working Paper | ||
| 520 | 3 | |a The adult mammalian heart is characterized by post-mitotic polyploid cardiomyocytes (CMs). Understanding how CMs regulate cell cycle exit and ploidy can help developing new heart regenerative therapies. Here, we uncover that the PIDDosome, a multi-protein complex activating the endopeptidase Caspase-2, helps to implement a CM-specific differentiation program that limits ploidy during postnatal heart development. DNA content analyses show that PIDDosome-loss causes a cell-autonomous increase in nuclear and cellular CM ploidy. Remarkably, increased ploidy does not affect cardiac structure nor function. PIDDosome-imposed ploidy restriction commences at postnatal day 7 (P7), reaching a plateau on P14. PIDDosome activation requires ANKRD26, targeting PIDD1 to mother centrioles. Opposite to prior observations in liver development, the PIDDosome limits CM polyploidization in a p53-independent manner but reliant on p21/Cdkn1a, a notion supported by nuclear RNA sequencing and genetic deletion experiments. Our results provide new insights how proliferation of polyploid CMs is restricted during postnatal heart development.Competing Interest StatementThe authors have declared no competing interest.Footnotes* We have included additional data, such as N-terminomics, aiming to identify Caspase-2 substrates, we also analyzed p73 KO mice. As a result, we also included additional authors | |
| 653 | |a p53 Protein | ||
| 653 | |a Polyploidy | ||
| 653 | |a Cell differentiation | ||
| 653 | |a Caspase-2 | ||
| 653 | |a Heart | ||
| 653 | |a Structure-function relationships | ||
| 653 | |a Cardiomyocytes | ||
| 653 | |a Ploidy | ||
| 653 | |a Centrioles | ||
| 653 | |a Postpartum period | ||
| 653 | |a Cell cycle | ||
| 700 | 1 | |a Eichin, Felix | |
| 700 | 1 | |a Kinz, Nadine | |
| 700 | 1 | |a Obwegs, David | |
| 700 | 1 | |a Sladky, Valentina C | |
| 700 | 1 | |a Rizzotto, Dario | |
| 700 | 1 | |a Manzl, Claudia | |
| 700 | 1 | |a Moos, Katharina | |
| 700 | 1 | |a Mergner, Julia | |
| 700 | 1 | |a Savko, Clarissa | |
| 700 | 1 | |a Giansanti, Piero | |
| 700 | 1 | |a Nicole Martinez Garcia | |
| 700 | 1 | |a Marques, Margarita M | |
| 700 | 1 | |a Jacotot, Etienne D | |
| 700 | 1 | |a Boerries, Melanie | |
| 700 | 1 | |a Sussman, Mark | |
| 700 | 1 | |a Villunger, Andreas | |
| 773 | 0 | |t bioRxiv |g (Feb 19, 2025) | |
| 786 | 0 | |d ProQuest |t Biological Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3168488963/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3168488963/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full text outside of ProQuest |u https://www.biorxiv.org/content/10.1101/2024.08.27.609375v2 |