Matches in SemOpenAlex for { <https://semopenalex.org/work/W3094351421> ?p ?o ?g. }
- W3094351421 abstract "Direct reprogramming of fibroblasts to alternative cell fates by forced expression of transcription factors offers a platform to explore fundamental molecular events governing cell fate identity. The discovery and study of induced cardiomyocytes (iCMs) not only provides alternative therapeutic strategies for heart disease but also sheds lights on basic biology underlying CM fate determination. The iCM field has primarily focused on early transcriptome and epigenome repatterning, whereas little is known about how reprogramming iCMs remodel, erase, and exit the initial fibroblast lineage to acquire final cell identity. Here, we show that autophagy-related 5 (Atg5)-dependent autophagy, an evolutionarily conserved self-digestion process, was induced and required for iCM reprogramming. Unexpectedly, the autophagic factor Beclin1 (Becn1) was found to suppress iCM induction in an autophagy-independent manner. Depletion of Becn1 resulted in improved iCM induction from both murine and human fibroblasts. In a mouse genetic model, Becn1 haploinsufficiency further enhanced reprogramming factor-mediated heart function recovery and scar size reduction after myocardial infarction. Mechanistically, loss of Becn1 up-regulated Lef1 and down-regulated Wnt inhibitors, leading to activation of the canonical Wnt/β-catenin signaling pathway. In addition, Becn1 physically interacts with other classical class III phosphatidylinositol 3-kinase (PI3K III) complex components, the knockdown of which phenocopied Becn1 depletion in cardiac reprogramming. Collectively, our study revealed an inductive role of Atg5-dependent autophagy as well as a previously unrecognized autophagy-independent inhibitory function of Becn1 in iCM reprogramming." @default.
- W3094351421 created "2020-10-29" @default.
- W3094351421 creator A5002533960 @default.
- W3094351421 creator A5008604223 @default.
- W3094351421 creator A5012278873 @default.
- W3094351421 creator A5014085457 @default.
- W3094351421 creator A5014942240 @default.
- W3094351421 creator A5028481056 @default.
- W3094351421 creator A5032493673 @default.
- W3094351421 creator A5034321470 @default.
- W3094351421 creator A5043257441 @default.
- W3094351421 creator A5051065426 @default.
- W3094351421 creator A5052586478 @default.
- W3094351421 creator A5065342163 @default.
- W3094351421 creator A5067006288 @default.
- W3094351421 creator A5068043631 @default.
- W3094351421 creator A5071927644 @default.
- W3094351421 creator A5084410970 @default.
- W3094351421 creator A5091527776 @default.
- W3094351421 date "2020-10-21" @default.
- W3094351421 modified "2023-10-16" @default.
- W3094351421 title "Down-regulation of Beclin1 promotes direct cardiac reprogramming" @default.
- W3094351421 cites W1499338046 @default.
- W3094351421 cites W1531821806 @default.
- W3094351421 cites W1780295430 @default.
- W3094351421 cites W1894319381 @default.
- W3094351421 cites W1965451377 @default.
- W3094351421 cites W1970637701 @default.
- W3094351421 cites W1976761774 @default.
- W3094351421 cites W1979339081 @default.
- W3094351421 cites W1979594866 @default.
- W3094351421 cites W1983831622 @default.
- W3094351421 cites W1987618226 @default.
- W3094351421 cites W1992659717 @default.
- W3094351421 cites W1999211990 @default.
- W3094351421 cites W2000723562 @default.
- W3094351421 cites W2017779665 @default.
- W3094351421 cites W2025665129 @default.
- W3094351421 cites W2035006418 @default.
- W3094351421 cites W2046250764 @default.
- W3094351421 cites W2058408625 @default.
- W3094351421 cites W2058553784 @default.
- W3094351421 cites W2058950912 @default.
- W3094351421 cites W2061870770 @default.
- W3094351421 cites W2064381459 @default.
- W3094351421 cites W2066697766 @default.
- W3094351421 cites W2066800765 @default.
- W3094351421 cites W2069679898 @default.
- W3094351421 cites W2076486071 @default.
- W3094351421 cites W2077353205 @default.
- W3094351421 cites W2077418979 @default.
- W3094351421 cites W2079784916 @default.
- W3094351421 cites W2082714048 @default.
- W3094351421 cites W2090916626 @default.
- W3094351421 cites W2098264151 @default.
- W3094351421 cites W2100024219 @default.
- W3094351421 cites W2100172364 @default.
- W3094351421 cites W2108234281 @default.
- W3094351421 cites W2108668124 @default.
- W3094351421 cites W2108862261 @default.
- W3094351421 cites W2111567059 @default.
- W3094351421 cites W2115886998 @default.
- W3094351421 cites W2117119983 @default.
- W3094351421 cites W2125987139 @default.
- W3094351421 cites W2130410032 @default.
- W3094351421 cites W2130682212 @default.
- W3094351421 cites W2131884100 @default.
- W3094351421 cites W2135767680 @default.
- W3094351421 cites W2135914580 @default.
- W3094351421 cites W2136541538 @default.
- W3094351421 cites W2138207763 @default.
- W3094351421 cites W2138977668 @default.
- W3094351421 cites W2142360968 @default.
- W3094351421 cites W2142974760 @default.
- W3094351421 cites W2156140279 @default.
- W3094351421 cites W2163170981 @default.
- W3094351421 cites W2165027208 @default.
- W3094351421 cites W2165451118 @default.
- W3094351421 cites W2166443964 @default.
- W3094351421 cites W2167202160 @default.
- W3094351421 cites W2170551349 @default.
- W3094351421 cites W2171808845 @default.
- W3094351421 cites W2179438025 @default.
- W3094351421 cites W2193208524 @default.
- W3094351421 cites W2197424077 @default.
- W3094351421 cites W2224270925 @default.
- W3094351421 cites W2235428790 @default.
- W3094351421 cites W2278964323 @default.
- W3094351421 cites W2284306073 @default.
- W3094351421 cites W2290864968 @default.
- W3094351421 cites W2330972395 @default.
- W3094351421 cites W2341539131 @default.
- W3094351421 cites W2531674790 @default.
- W3094351421 cites W2554457530 @default.
- W3094351421 cites W2593494308 @default.
- W3094351421 cites W2752326209 @default.
- W3094351421 cites W2760573373 @default.
- W3094351421 cites W2763345483 @default.
- W3094351421 cites W2765457511 @default.
- W3094351421 cites W2767103112 @default.