Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes

被引:26
作者
Kim, Tae Kyung [1 ]
Sul, Jai-Yoon [1 ]
Peternko, Nataliya B. [2 ,3 ]
Lee, Jae Hee [1 ]
Lee, Miler [4 ,5 ]
Patel, Vickas V. [2 ,3 ]
Kim, Junhyong [4 ,5 ]
Eberwine, James H. [1 ,5 ]
机构
[1] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Med, Dept Biol, Philadelphia, PA 19104 USA
[5] Univ Penn, Sch Med, Penn Genome Frontiers Inst, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
relative abundance; lipid-mediated; TIPeR; microarray; patch clamp; PLURIPOTENT STEM-CELLS; FUNCTIONAL CARDIOMYOCYTES; SOMATIC-CELLS; FIBROBLASTS; HEART; DIFFERENTIATION; GENERATION; OCT4; BIOINFORMATICS; INDUCTION;
D O I
10.1073/pnas.1101223108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We show that the transfer of the adult ventricular myocyte (AVM) transcriptome into either a fibroblast or an astrocyte converts the host cell into a cardiomyocyte. Transcriptome-effected cardiomyocytes (tCardiomyocytes) display morphologies, immunocytochemical properties, and expression profiles of postnatal cardiomyocytes. Cell morphology analysis shows that tCardiomyoctes are elongated and have a similar length-to-width ratio as AVMs. These global phenotypic changes occur in a time-dependent manner and confer electroexcitability to the tCardiomyocytes. tCardiomyocyte generation does not require continuous overexpression of specific transcription factors; for example, the expression level of transcription factor Mef2c is higher in tCardiomyocytes than in fibroblasts, but similar in tCardiomyocytes and AVMs. These data highlight the dominant role of the gene expression profile in developing and maintaining cellular phenotype. The transcriptome-induced phenotype remodeling-generated tCardiomyocyte has significant implications for understanding and modulating cardiac disease development.
引用
收藏
页码:11918 / 11923
页数:6
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