Howard Hughes Medical Institute and Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, Cambridge, Massachusetts, USA.
Nat Biotechnol. 2010 Aug;28(8):848-55. doi: 10.1038/nbt.1667. Epub 2010 Jul 19.
Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.
诱导多能干细胞（iPSCs）已通过异位表达特定因子从各种体细胞群中获得。目前尚不清楚是否从不同细胞类型产生的 iPSCs 在分子和功能上相似。在这里，我们证明了从小鼠成纤维细胞、造血细胞和肌细胞中获得的 iPSCs 表现出不同的转录组和表观遗传模式。此外，我们证明了细胞起源影响 iPSCs 向胚状体和不同造血细胞类型体外分化的潜力。值得注意的是，iPSCs 的连续传代会大大减弱这些差异。我们的研究结果表明，早期传代的 iPSCs 保留了其体细胞来源的短暂的表观遗传记忆，表现为差异基因表达和改变的分化能力。这些观察结果可能会影响目前使用 iPSCs 进行疾病建模的尝试，也可能在潜在的治疗应用中得到利用，以增强向所需细胞谱系的分化。
