Department of Developmental Biology, University of Pittsburgh, 530 45th Street, 8117 Rangos Research Center, Pittsburgh, PA 15201, USA.
Stem Cell Res Ther. 2011 Jan 14;2(1):1. doi: 10.1186/scrt42.
Recent advances in stem cell biology have established the feasibility of reprogramming human and murine fibroblast cells into induced pluripotent stem cells. Three master regulators have been demonstrated to be sufficient in the management of cell status of 'pluripotent' versus 'differentiated'. The same strategy has been used to directly convert one somatic cell type into another cell type, such as the converting of exocrine pancreas cells into cells closely resembling beta cells and the reprogramming of fibroblast cells into functional neuron cells. Srivastava's group reported the first direct reprogramming of mouse fibroblast cells into mesoderm lineage cells (cardiomyocytes) with the enforced expression of three cardiac transcriptional factors: Gata4, Mef2c, and Tbx5. The induced cardiomyocytes exhibit a global gene expression profile and basic electrophysiological characteristics similar to those of postnatal cardiomyocytes. This study made significant advances in cardiovascular and stem cell fields and has important implications in understanding heart developmental biology as well as in potential therapies of human cardiovascular diseases.
近年来，干细胞生物学的进展已经确立了将人类和鼠类成纤维细胞重编程为诱导多能干细胞的可行性。已经证明，有三个主要的调控因子足以管理细胞的“多能性”与“分化”状态。同样的策略也被用于直接将一种体细胞类型转化为另一种细胞类型，例如将外分泌胰腺细胞转化为类似于β细胞的细胞，以及将成纤维细胞重编程为功能性神经元细胞。Srivastava 的研究小组报告了首例通过强制表达三种心脏转录因子（Gata4、Mef2c 和 Tbx5）将小鼠成纤维细胞直接重编程为中胚层谱系细胞（心肌细胞）的研究。诱导的心肌细胞表现出与出生后心肌细胞相似的全基因组表达谱和基本电生理特征。这项研究在心血管和干细胞领域取得了重大进展，对于理解心脏发育生物学以及人类心血管疾病的潜在治疗方法具有重要意义。
