Department of Pharmacology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11918-23. doi: 10.1073/pnas.1101223108. Epub 2011 Jul 5.
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.
我们证明，将成人心室肌细胞（AVM）的转录组转移到成纤维细胞或星形胶质细胞中，会将宿主细胞转化为心肌细胞。转录组效应心肌细胞（t 心肌细胞）表现出形态、免疫细胞化学特性和出生后心肌细胞的表达谱。细胞形态分析表明，t 心肌细胞呈长形，长宽比与 AVM 相似。这些全局表型变化呈时间依赖性，并赋予 t 心肌细胞电兴奋性。t 心肌细胞的产生不需要持续过表达特定的转录因子；例如，转录因子 Mef2c 在 t 心肌细胞中的表达水平高于成纤维细胞，但在 t 心肌细胞和 AVM 中相似。这些数据突出了基因表达谱在发育和维持细胞表型中的主导作用。转录组诱导的表型重塑产生的 t 心肌细胞对理解和调节心脏疾病的发展具有重要意义。
