Sublethal caspase activation promotes generation of cardiomyocytes from embryonic stem cells.
Sublethal caspase activation promotes generation of cardiomyocytes from embryonic stem cells.
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DOI：
10.1371/journal.pone.0120176
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Grinnemo KH
中科院分区：
文献类型：
--
作者：
Bulatovic I;Ibarra C;Österholm C;Wang H;Beltrán-Rodríguez A;Varas-Godoy M;Månsson-Broberg A;Uhlén P;Simon A;Grinnemo KH
新生心肌细胞的产生对于心肌损伤后的心脏修复至关重要，但哪种刺激对心肌细胞再生最重要仍不清楚。在这里，我们探讨，如果凋亡刺激，表现为通过半胱天冬酶激活，影响心脏祖细胞上调和心肌细胞分化。以小鼠胚胎干细胞为细胞模型，我们发现半胱天冬酶的亚致死激活增加了心肌细胞的产量，同时促进了c-Kit+/α-actininlow心脏祖细胞的增殖和分化。广谱半胱天冬酶抑制剂阻断了这些作用。此外，半胱天冬酶抑制剂逆转心肌细胞及其前体细胞中表达的基因的mRNA表达。我们的研究表明，亚致死半胱天冬酶激活在心肌细胞分化中具有重要作用，并可能对促进外源性或内源性细胞来源的心肌损伤后的心脏再生具有重要意义。
Generation of new cardiomyocytes is critical for cardiac repair following myocardial injury, but which kind of stimuli is most important for cardiomyocyte regeneration is still unclear. Here we explore if apoptotic stimuli, manifested through caspase activation, influences cardiac progenitor up-regulation and cardiomyocyte differentiation. Using mouse embryonic stem cells as a cellular model, we show that sublethal activation of caspases increases the yield of cardiomyocytes while concurrently promoting the proliferation and differentiation of c-Kit+/α-actininlow cardiac progenitor cells. A broad-spectrum caspase inhibitor blocked these effects. In addition, the caspase inhibitor reversed the mRNA expression of genes expressed in cardiomyocytes and their precursors. Our study demonstrates that sublethal caspase-activation has an important role in cardiomyocyte differentiation and may have significant implications for promoting cardiac regeneration after myocardial injury involving exogenous or endogenous cell sources.
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影响因子：
11.8
作者：
Arama, E;Agapite, J;Steller, H
通讯作者：
Steller, H
影响因子：
4.8
作者：
Akbari-Birgani, Shiva;Hosseinkhani, Saman;Baharvand, Hossein
通讯作者：
Baharvand, Hossein
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Ellison, Georgina M.;Vicinanza, Carla;Nadal-Ginard, Bernardo
通讯作者：
Nadal-Ginard, Bernardo
影响因子：
4.8
作者：
Fernando, P;Brunette, S;Megeney, LA
通讯作者：
Megeney, LA