Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog.
We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventual goal of clinical application it is necessary to develop new methodologies to overcome these limitations. Here, we report the identification of a specific media composition, reprogramming media (RM), which augmented the effect of miR combo by 5-15-fold depending upon the cardiac marker tested. RM alone was sufficient to strongly induce cardiac gene and protein expression in neonatal tail-tip as well as cardiac fibroblasts. Expression of pluripotency markers Nanog, Oct4, Sox2, and Klf4 was significantly enhanced by RM, with miR combo augmenting the effect further. Knockdown of Nanog by siRNA inhibited the effect of RM on cardiac gene expression. Removal of insulin-transferrin-selenium completely inhibited the effect of reprogramming media upon cardiac gene expression and the addition of selenium to standard culture media recapitulated the effects of RM. Moreover, selenium enhanced the reprogramming efficiency of miR combo.
Duke Scholars
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- Transferrins
- Selenium
- SOXB1 Transcription Factors
- Reverse Transcriptase Polymerase Chain Reaction
- RNA Interference
- Octamer Transcription Factor-3
- Nanog Homeobox Protein
- Myocytes, Cardiac
- MicroRNAs
- Mice, Inbred C57BL
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Transferrins
- Selenium
- SOXB1 Transcription Factors
- Reverse Transcriptase Polymerase Chain Reaction
- RNA Interference
- Octamer Transcription Factor-3
- Nanog Homeobox Protein
- Myocytes, Cardiac
- MicroRNAs
- Mice, Inbred C57BL