English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Background  Reprogramming of cardiac fibroblasts into induced cardiomyocyte‐like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies.    Methods and Results  Lentivirus vectors expressing Gata4, Mef2c, and Tbx5 ( GMT ); Hand2 (H), Myocardin (My), or microRNA (miR)‐590 were administered to rat, porcine, and human cardiac fibroblasts in vitro. induced cardiomyocyte‐like cell production was then evaluated by assessing expression of the cardiomyocyte marker, cardiac troponin T ( cTnT ), whereas signaling pathway studies were performed to identify reprogramming factor targets.  GMT  administration induced  cTnT  expression in ≈6% of rat fibroblasts, but failed to induce  cTnT  expression in porcine or human cardiac fibroblasts. Addition of H/My and/or miR‐590 to  GMT  administration resulted in  cTNT  expression in ≈5% of porcine and human fibroblasts and also upregulated the expression of the cardiac genes,  MYH 6 and  TNNT 2. When cocultured with murine cardiomyocytes,  cTnT ‐expressing porcine cardiac fibroblasts exhibited spontaneous contractions. Administration of  GMT  plus either H/My or miR‐590 alone also downregulated fibroblast genes  COL 1A1 and  COL 3A1. miR‐590 was shown to directly suppress the zinc finger protein, specificity protein 1 (Sp1), which was able to substitute for miR‐590 in inducing cellular reprogramming.    Conclusions  These data support porcine studies as a surrogate for testing human cardiac reprogramming, and suggest that miR‐590‐mediated repression of Sp1 represents an alternative pathway for enhancing human cardiac cellular reprogramming.

MiR‐590 Promotes Transdifferentiation of Porcine and Human Fibroblasts Toward a Cardiomyocyte‐Like Fate by Directly Repressing Specificity Protein 1