---
_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:
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pmid:
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publication_identifier:
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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'
...