2017
DOI: 10.1161/circulationaha.116.024692
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Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming

Abstract: Background Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ represents a promising strategy for cardiac regeneration. A combination of three cardiac transcription factors, Gata4, Mef2c and Tbx5 (GMT), can convert fibroblasts into iCMs, albeit with low efficiency in vitro. Methods We screened 5,500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming. Results We found that a combination of the … Show more

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Cited by 208 publications
(240 citation statements)
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“…At the same time, the success of our approach (a 1-wk delay in drug delivery following injury) reveals at a minimum a 1-wk window in which initiation of Porcn inhibitor delivery following myocardial infarction (MI) might be beneficial. Finally, we acknowledge that changes in the expression of Col6 may be only one proregenerative consequence of Porcn inhibition and that other molecular changes (38,39) may also be factors that influence heart function outcome.…”
Section: Discussionmentioning
confidence: 98%
“…At the same time, the success of our approach (a 1-wk delay in drug delivery following injury) reveals at a minimum a 1-wk window in which initiation of Porcn inhibitor delivery following myocardial infarction (MI) might be beneficial. Finally, we acknowledge that changes in the expression of Col6 may be only one proregenerative consequence of Porcn inhibition and that other molecular changes (38,39) may also be factors that influence heart function outcome.…”
Section: Discussionmentioning
confidence: 98%
“…Mouse transthoracic echocardiograms were performed as previously described (Mohamed et al, 2016). Briefly, mice were anesthetized with isoflurane, placed on a heating pad, and ventral fur shaved with clippers.…”
Section: Star Methodsmentioning
confidence: 99%
“…Another feature to consider is that humans have a longer developmental time than mice, potentially contributing to the species differences in cell reprogramming. Interestingly, despite the requirement of different factors for direct cardiac reprogramming between species, crucial endogenous signalling pathways such as the TGFβ1 and WNT signalling pathways contribute similarly to cardiac reprogramming in both mouse and human cells 120 .…”
Section: Direct Reprogramming For Heart Repairmentioning
confidence: 99%