Reprogramming

Inflammation and cardiac reprogramming

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Science  27 Oct 2017:
Vol. 358, Issue 6362, pp. 494
DOI: 10.1126/science.358.6362.494-b

Tissue repair after a heart attack is a balance between inflammation to remove cell debris and active cell regeneration. Intervening in cell replacement and reprogramming thus offers therapeutic options to promote healing with minimal scar formation by fibroblasts. However, reprogramming of adult fibroblasts into pulsatile cardiomyocytes is not straightforward. To improve the reprogramming protocol, Zhou et al. performed an unbiased screen of 786 transcription factors, epigenetic regulators, cytokines, and nuclear receptors. The screen identified a transcription factor (ZNF281) that associates with the essential cardiac development transcription factor GATA4 to stimulate cardiac reprogramming and suppress inflammatory signaling. Anti-inflammatory drugs also stimulate cardiac gene expression. ZNF281 appears to act at a nexus between cardiac and inflammatory gene programs that exert opposite influences on fibroblast reprogramming.

Genes Dev. 10.1101/gad.305482.117 (2017).

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