--- _id: '9874' abstract: - lang: eng text: Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. Here we report that the miR-106b~25 cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. In line, gene delivery of miR-106b~25 to the mouse heart provokes cardiomyocyte proliferation by targeting a network of negative cell cycle regulators including E2f5, Cdkn1c, Ccne1 and Wee1. Conversely, gene-targeted miR-106b~25 null mice display spontaneous hypertrophic remodeling and exaggerated remodeling to overload by derepression of the prohypertrophic transcription factors Hand2 and Mef2d. Taking advantage of the regulatory function of miR-106b~25 on cardiomyocyte hyperplasia and hypertrophy, viral gene delivery of miR-106b~25 provokes nearly complete regeneration of the adult myocardium after ischemic injury. Our data demonstrate that exploitation of conserved molecular programs can enhance the regenerative capacity of the injured heart. acknowledgement: E.D. is supported by a VENI award 916-150-16 from the Netherlands Organization for Health Research and Development (ZonMW), an EMBO Long-term Fellowship (EMBO ALTF 848-2013) and a FP7 Marie Curie Intra-European Fellowship (Project number 627539). V.S.P. was funded by a fellowship from the FCT/ Ministério da Ciência, Tecnologia e Inovação SFRH/BD/111799/2015. P.D.C.M. is an Established Investigator of the Dutch Heart Foundation. L.D.W. acknowledges support from the Dutch CardioVascular Alliance (ARENA-PRIME). L.D.W. was further supported by grant 311549 from the European Research Council (ERC), a VICI award 918-156-47 from the Dutch Research Council and Marie Sklodowska-Curie grant agreement no. 813716 (TRAIN-HEART). article_number: '4808' article_processing_charge: Yes article_type: original author: - first_name: Andrea full_name: Raso, Andrea last_name: Raso - first_name: Ellen full_name: Dirkx, Ellen last_name: Dirkx - first_name: Vasco full_name: Sampaio-Pinto, Vasco last_name: Sampaio-Pinto - first_name: Hamid full_name: el Azzouzi, Hamid last_name: el Azzouzi - first_name: Ryan J full_name: Cubero, Ryan J id: 850B2E12-9CD4-11E9-837F-E719E6697425 last_name: Cubero orcid: 0000-0003-0002-1867 - first_name: Daniel W. full_name: Sorensen, Daniel W. last_name: Sorensen - first_name: Lara full_name: Ottaviani, Lara last_name: Ottaviani - first_name: Servé full_name: Olieslagers, Servé last_name: Olieslagers - first_name: Manon M. full_name: Huibers, Manon M. last_name: Huibers - first_name: Roel full_name: de Weger, Roel last_name: de Weger - first_name: Sailay full_name: Siddiqi, Sailay last_name: Siddiqi - first_name: Silvia full_name: Moimas, Silvia last_name: Moimas - first_name: Consuelo full_name: Torrini, Consuelo last_name: Torrini - first_name: Lorena full_name: Zentillin, Lorena last_name: Zentillin - first_name: Luca full_name: Braga, Luca last_name: Braga - first_name: Diana S. full_name: Nascimento, Diana S. last_name: Nascimento - first_name: Paula A. full_name: da Costa Martins, Paula A. last_name: da Costa Martins - first_name: Jop H. full_name: van Berlo, Jop H. last_name: van Berlo - first_name: Serena full_name: Zacchigna, Serena last_name: Zacchigna - first_name: Mauro full_name: Giacca, Mauro last_name: Giacca - first_name: Leon J. full_name: De Windt, Leon J. last_name: De Windt citation: ama: Raso A, Dirkx E, Sampaio-Pinto V, et al. A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration. Nature Communications. 2021;12. doi:10.1038/s41467-021-25211-4 apa: Raso, A., Dirkx, E., Sampaio-Pinto, V., el Azzouzi, H., Cubero, R. J., Sorensen, D. W., … De Windt, L. J. (2021). A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-25211-4 chicago: Raso, Andrea, Ellen Dirkx, Vasco Sampaio-Pinto, Hamid el Azzouzi, Ryan J Cubero, Daniel W. Sorensen, Lara Ottaviani, et al. “A MicroRNA Program Regulates the Balance between Cardiomyocyte Hyperplasia and Hypertrophy and Stimulates Cardiac Regeneration.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-25211-4. ieee: A. Raso et al., “A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration,” Nature Communications, vol. 12. Springer Nature, 2021. ista: Raso A, Dirkx E, Sampaio-Pinto V, el Azzouzi H, Cubero RJ, Sorensen DW, Ottaviani L, Olieslagers S, Huibers MM, de Weger R, Siddiqi S, Moimas S, Torrini C, Zentillin L, Braga L, Nascimento DS, da Costa Martins PA, van Berlo JH, Zacchigna S, Giacca M, De Windt LJ. 2021. A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration. Nature Communications. 12, 4808. mla: Raso, Andrea, et al. “A MicroRNA Program Regulates the Balance between Cardiomyocyte Hyperplasia and Hypertrophy and Stimulates Cardiac Regeneration.” Nature Communications, vol. 12, 4808, Springer Nature, 2021, doi:10.1038/s41467-021-25211-4. short: A. Raso, E. Dirkx, V. Sampaio-Pinto, H. el Azzouzi, R.J. Cubero, D.W. Sorensen, L. Ottaviani, S. Olieslagers, M.M. Huibers, R. de Weger, S. Siddiqi, S. Moimas, C. Torrini, L. Zentillin, L. Braga, D.S. Nascimento, P.A. da Costa Martins, J.H. van Berlo, S. Zacchigna, M. Giacca, L.J. De Windt, Nature Communications 12 (2021). date_created: 2021-08-10T11:49:20Z date_published: 2021-08-10T00:00:00Z date_updated: 2023-08-11T10:27:03Z day: '10' ddc: - '610' - '570' department: - _id: SaSi doi: 10.1038/s41467-021-25211-4 external_id: isi: - '000683910200042' pmid: - '34376683' file: - access_level: open_access checksum: 48d8562e8229e4282f3f354b329722c5 content_type: application/pdf creator: asandaue date_created: 2021-08-10T12:29:59Z date_updated: 2021-08-10T12:29:59Z file_id: '9876' file_name: 2021_NatureCommunications_Raso.pdf file_size: 4364333 relation: main_file success: 1 file_date_updated: 2021-08-10T12:29:59Z genbank: - GSE178867 has_accepted_license: '1' intvolume: ' 12' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1038/s41467-022-32785-0 scopus_import: '1' status: public title: A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ...