Cell Biology and Neurobiology Institute, National Research Council of Italy, Roma, Italy.
Cell Death Differ. 2012 Jul;19(7):1162-74. doi: 10.1038/cdd.2011.205. Epub 2012 Jan 20.
Adult mammalian cells can be reprogrammed to a pluripotent state by forcing the expression of a few embryonic transcription factors. The resulting induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers. It is well known that post-natal cardiomyocytes (CMs) lack the capacity to proliferate. Here, we report that neonatal CMs can be reprogrammed to generate iPS cells that express embryonic-specific markers and feature gene-expression profiles similar to those of mouse embryonic stem (mES) cell and cardiac fibroblast (CF)-derived iPS cell populations. CM-derived iPS cells are able to generate chimeric mice and, moreover, re-differentiate toward CMs more efficiently then either CF-derived iPS cells or mES cells. The increased differentiation capacity is possibly related to CM-derived iPS cells retaining an epigenetic memory of the phenotype of their founder cell. CM-derived iPS cells may thus lead to new information on differentiation processes underlying cardiac differentiation and proliferation.
成体细胞可通过强制表达少数几种胚胎转录因子重编程为多能状态。由此产生的诱导多能干细胞(iPS 细胞)可分化为所有三个胚层的细胞。众所周知,出生后的心肌细胞(CM)缺乏增殖能力。在这里,我们报告说,新生儿 CM 可被重编程为产生表达胚胎特异性标记物的 iPS 细胞,并具有与小鼠胚胎干细胞(mES)细胞和心脏成纤维细胞(CF)衍生的 iPS 细胞群体相似的基因表达谱。CM 衍生的 iPS 细胞能够生成嵌合小鼠,并且比 CF 衍生的 iPS 细胞或 mES 细胞更有效地重新分化为 CM。分化能力的增加可能与 CM 衍生的 iPS 细胞保留了其起始细胞表型的表观遗传记忆有关。因此,CM 衍生的 iPS 细胞可能会为心脏分化和增殖的分化过程提供新的信息。