In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes.

In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes.
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DOI:
10.1038/s42003-021-02677-y
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发表时间:
2021-09-30
影响因子:
5.9
通讯作者:
Cianflone E
Cianflone E
中科院分区:
生物学2区
文献类型:
--
作者:
Scalise M;Marino F;Salerno L;Mancuso T;Cappetta D;Barone A;Parrotta EI;Torella A;Palumbo D;Veltri P;De Angelis A;Berrino L;Rossi F;Weisz A;Rota M;Urbanek K;Nadal-Ginard B;Torella D;Cianflone E

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miRNA通过靶向细胞周期调节因子的mRNA并在心肌谱系基因调控环中起作用来调节心肌细胞的特化。目前尚不清楚这些miRNA/mRNA网络是否或在多大程度上在成体心脏干/祖细胞(CSC)的心肌细胞分化过程中起作用。克隆来源的小鼠CSC在体外分化为收缩心肌细胞(iCM)。“CSC vs. iCM”mRNome和microRNome的比较显示CM相关mRNA的平衡上调以及细胞周期和DNA复制mRNA的下调。iCM中细胞周期基因的下调和成熟肌丝基因的上调达到介于胎儿和新生心肌细胞之间的水平。心肌miR在iCM中上调。在iCM中起作用的miRNA/mRNA的特定网络与成人CM(aCM)的那些非常相似。miR-1和miR-499增强iCM向终末分化的成肌定型。总之,CSC特化/分化为收缩iCM遵循已知的心肌-MiR依赖性发育心肌细胞分化轨迹,iCM转录组/miRNome类似于CM。Scalise等人检查了从鼠成体心脏干细胞(CSC)分化的心肌细胞的mRNA组和miRNA组。他们的结果表明,分化过程遵循与成年心肌细胞相似的miRNA/mRNA表达轨迹。
miRNAs modulate cardiomyocyte specification by targeting mRNAs of cell cycle regulators and acting in cardiac muscle lineage gene regulatory loops. It is unknown if or to-what-extent these miRNA/mRNA networks are operative during cardiomyocyte differentiation of adult cardiac stem/progenitor cells (CSCs). Clonally-derived mouse CSCs differentiated into contracting cardiomyocytes in vitro (iCMs). Comparison of “CSCs vs. iCMs” mRNome and microRNome showed a balanced up-regulation of CM-related mRNAs together with a down-regulation of cell cycle and DNA replication mRNAs. The down-regulation of cell cycle genes and the up-regulation of the mature myofilament genes in iCMs reached intermediate levels between those of fetal and neonatal cardiomyocytes. Cardiomyo-miRs were up-regulated in iCMs. The specific networks of miRNA/mRNAs operative in iCMs closely resembled those of adult CMs (aCMs). miR-1 and miR-499 enhanced myogenic commitment toward terminal differentiation of iCMs. In conclusions, CSC specification/differentiation into contracting iCMs follows known cardiomyo-MiR-dependent developmental cardiomyocyte differentiation trajectories and iCMs transcriptome/miRNome resembles that of CMs. Scalise et al. examine the mRNAome and miRNAome of cardiomyocytes differentiated from murine adult cardiac stem cells (CSCs). Their results show that the differentiation process follows a trajectory of miRNA/mRNA expression that resembles that of adult cardiomyocytes.
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