Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell Res. 2012 Jan;22(1):178-93. doi: 10.1038/cr.2011.133. Epub 2011 Aug 16.
While it is clear that human pluripotent stem cells (hPSCs) can differentiate to generate a panoply of various cell types, it is unknown how closely in vitro development mirrors that which occurs in vivo. To determine whether human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) make equivalent progeny, and whether either makes cells that are analogous to tissue-derived cells, we performed comprehensive transcriptome profiling of purified PSC derivatives and their tissue-derived counterparts. Expression profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for the neural, hepatic, and mesenchymal lineages, and an absence of re-expression from exogenous reprogramming factors in hiPSC progeny. However, when compared to a tissue-derived counterpart, the progeny of both hESCs and hiPSCs maintained expression of a subset of genes normally associated with early mammalian development, regardless of the type of cell generated. While pluripotent genes (OCT4, SOX2, REX1, and NANOG) appeared to be silenced immediately upon differentiation from hPSCs, genes normally unique to early embryos (LIN28A, LIN28B, DPPA4, and others) were not fully silenced in hPSC derivatives. These data and evidence from expression patterns in early human fetal tissue (3-16 weeks of development) suggest that the differentiated progeny of hPSCs are reflective of very early human development (< 6 weeks). These findings provide support for the idea that hPSCs can serve as useful in vitro models of early human development, but also raise important issues for disease modeling and the clinical application of hPSC derivatives.
虽然人类多能干细胞（hPSCs）可以分化生成各种细胞类型，但尚不清楚体外发育与体内发育的相似度。为了确定人类胚胎干细胞（hESCs）和人类诱导多能干细胞（hiPSCs）是否产生等同的后代，以及它们是否生成与组织衍生细胞类似的细胞，我们对纯化的 PSC 衍生物及其组织衍生对应物进行了全面的转录组谱分析。表达谱分析表明，hESCs 和 hiPSCs 在神经、肝和间充质谱系中产生几乎相同的后代，并且在 hiPSC 后代中不存在来自外源性重编程因子的再表达。然而，与组织衍生的对应物相比，hESCs 和 hiPSCs 的后代都保留了一组通常与早期哺乳动物发育相关的基因的表达，无论生成的细胞类型如何。虽然多能基因（OCT4、SOX2、REX1 和 NANOG）似乎在 hPSCs 分化后立即被沉默，但在 hPSC 衍生物中，正常情况下仅存在于早期胚胎中的基因（LIN28A、LIN28B、DPPA4 等）并未完全沉默。这些数据以及来自早期人类胎儿组织（3-16 周发育）的表达模式的证据表明，hPSCs 的分化后代反映了非常早期的人类发育（<6 周）。这些发现为 hPSCs 可作为早期人类发育的有用体外模型提供了支持，但也为疾病建模和 hPSC 衍生物的临床应用提出了重要问题。
