Meis1 regulates postnatal cardiomyocyte cell cycle arrest
The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:497 |
|---|---|
| Enthalten in: |
Nature - 497(2013), 7448 vom: 09. Mai, Seite 249-253 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Mahmoud, Ahmed I [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 30.05.2013 Date Revised 21.10.2021 published: Print-Electronic CommentIn: Cell Res. 2013 Aug;23(8):978-9. - PMID 23774267 Citation Status MEDLINE |
|---|
| doi: |
10.1038/nature12054 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM226760197 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM226760197 | ||
| 003 | DE-627 | ||
| 005 | 20231224072139.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/nature12054 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0756.xml |
| 035 | |a (DE-627)NLM226760197 | ||
| 035 | |a (NLM)23594737 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Mahmoud, Ahmed I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Meis1 regulates postnatal cardiomyocyte cell cycle arrest |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.05.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Cell Res. 2013 Aug;23(8):978-9. - PMID 23774267 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p15 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p16 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p21 |2 NLM | |
| 650 | 7 | |a Homeodomain Proteins |2 NLM | |
| 650 | 7 | |a Meis1 protein, mouse |2 NLM | |
| 650 | 7 | |a Myeloid Ecotropic Viral Integration Site 1 Protein |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 700 | 1 | |a Kocabas, Fatih |e verfasserin |4 aut | |
| 700 | 1 | |a Muralidhar, Shalini A |e verfasserin |4 aut | |
| 700 | 1 | |a Kimura, Wataru |e verfasserin |4 aut | |
| 700 | 1 | |a Koura, Ahmed S |e verfasserin |4 aut | |
| 700 | 1 | |a Thet, Suwannee |e verfasserin |4 aut | |
| 700 | 1 | |a Porrello, Enzo R |e verfasserin |4 aut | |
| 700 | 1 | |a Sadek, Hesham A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature |d 1945 |g 497(2013), 7448 vom: 09. Mai, Seite 249-253 |w (DE-627)NLM000008257 |x 1476-4687 |7 nnns |
| 773 | 1 | 8 | |g volume:497 |g year:2013 |g number:7448 |g day:09 |g month:05 |g pages:249-253 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/nature12054 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 497 |j 2013 |e 7448 |b 09 |c 05 |h 249-253 | ||