Isoform Specific Effects of Mef2C during Direct Cardiac Reprogramming.
Mef2C protein
cardiac myocytes
fibroblasts
isoform
reprogramming
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
22 01 2020
22 01 2020
Historique:
received:
16
09
2019
revised:
13
01
2020
accepted:
20
01
2020
entrez:
26
1
2020
pubmed:
26
1
2020
medline:
12
2
2021
Statut:
epublish
Résumé
Direct conversion of cardiac fibroblasts into induced cardiomyocytes (iCMs) by forced expression of defined factors holds great potential for regenerative medicine by offering an alternative strategy for treatment of heart disease. Successful iCM conversion can be achieved by minimally using three transcription factors, Mef2c (M), Gata4(G), and Tbx5 (T). Despite increasing interest in iCM mechanistic studies using MGT(polycistronic construct with optimal expression of M,G and T), the reprogramming efficiency varies among different laboratories. Two main Mef2c isoforms (isoform2, Mi2 and isoform4, Mi4) are present in heart and are used separately by different labs, for iCM reprogramming. It is currently unknown if differently spliced isoform of Mef2c contributes to varied reprogramming efficiency. Here, we used Mi2 and Mi4 together with Gata4 and Tbx5 in separate vectors or polycistronic vector, to convert fibroblasts to iCMs. We found that Mi2 can induce higher reprogramming efficiency than Mi4 in MEFs. Addition of Hand2 to MGT retroviral cocktail or polycistronic Mi2-GT retroviruses further enhanced the iCM conversion. Overall, this study demonstrated the isoform specific effects of Mef2c, during iCM reprogramming, clarified some discrepancy about varied efficiency among labs and might lead to future research into the role of alternative splicing and the consequent variants in cell fate determination.
Identifiants
pubmed: 31979018
pii: cells9020268
doi: 10.3390/cells9020268
pmc: PMC7072587
pii:
doi:
Substances chimiques
MEF2 Transcription Factors
0
Protein Isoforms
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139976
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139880
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128331
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144551
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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