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Development:科学家发现驱动胚胎或成体心肌前体细胞向血管细胞命运转化的重要信号通路

2017-12-18 MedSci MedSci原创

Wnt信号通路在心肌细胞炎症、增殖和重塑等损伤修复过程中发挥着多种作用,但是这些作用也许可以归结为抑制Wnt信号能够促进成体CPCs向前血管的分化。

Wnt信号通路在胚胎心脏发生过程中扮演着多种角色。在许多人多能干细胞向心脏相关细胞分化体系中激活或抑制Wnt信号也尤为重要。然而,几乎没有研究揭示Wnt信号通路在心脏前体细胞进一步向下游分化中发挥的作用。科学家以转基因小鼠和人多能干细胞为模型,研究发现心脏内皮细胞来源于表达Nkx2.5的心脏前体细胞。在人多能干细胞向心肌分化的不同阶段分析具有内皮分化功能的心脏前体细胞,发现抑制Wnt信号的活性标志着内皮细胞的特化过程的开始。激活或者抑制Wnt信号通路分别能够增加或者减少CPC细胞群体中血管细胞的比例。Wnt5a在心脏发育过程中发挥着抑制Wnt信号通路的作用,它在来源于人多能干细胞的心肌前体细胞向内皮特化的过程中表达水平显着升高,并且外源的Wnt5a能够促进人多能干细胞和小鼠胚胎CPCs向血管内皮的特化过程。

尽管Wnt信号通路在心肌细胞炎症、增殖和重塑等损伤修复过程中发挥着多种作用,但是这些作用也许可以归结为抑制Wnt信号能够促进成体CPCs向前血管的分化。

原文来源:
Reichman D, Park L, Man L, et al. Wnt inhibition promotes vascular specification of embryonic cardiac progenitors[J]. Development, 2017: dev. 159905. DOI:10.1242/dev.159905

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    2018-04-15 fzwish20000
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    2017-12-20 ailian1202
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