Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.
Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.
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DOI：
10.1186/1471-213x-10-98
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发表时间：
2010-09-15
影响因子：
--
通讯作者：
Sarić T
中科院分区：
文献类型：
--
作者：
Gupta MK;Illich DJ;Gaarz A;Matzkies M;Nguemo F;Pfannkuche K;Liang H;Classen S;Reppel M;Schultze JL;Hescheler J;Sarić T
诱导多能干细胞（iPS）衍生的心肌细胞（CM）的功能和分子完整性对于其在组织修复、疾病建模和药物筛选中的应用是必不可少的。在这项研究中，我们比较了全球的跳动集群（BC）从分化的人iPS细胞和胚胎干细胞（ES）的显微切割转录组。层次聚类和主成分分析显示，iPS-BC和ES-BC聚类在一起，类似地富集心脏特异性基因，并且仅1.9%的本转录本的表达不同。类似地，iPS-CM的肌节组织、电生理特性和钙处理与ES-CM的肌节组织、电生理特性和钙处理没有区别。基因本体分析显示，在204个基因中，在iPS-BCs与ES-BCs中上调，与细胞外基质，细胞粘附和组织发育相关的过程被过度表达。有趣的是，在未分化的iPS与ES细胞中上调的106个基因中有47个在iPS-BC与ES-BC中仍然富集。发现这些基因中的大多数在用于重编程的成纤维细胞中高度表达，并且34%与最近报道的iPS细胞富集基因重叠。这些数据表明iPS-BC在转录上与ES-BC高度相似。然而，iPS-BC似乎与未分化的iPS细胞共享一些体细胞特征。因此，iPS-BC可能与ES-BC不完全相同。表达谱中的这些微小差异可能是由于iPS-BC和ES-BC的细胞组成差异、由于体细胞在分化的iPS细胞衍生物中的一些遗传谱的保留、或两者所致。
Functional and molecular integrity of cardiomyocytes (CMs) derived from induced pluripotent stem (iPS) cells is essential for their use in tissue repair, disease modelling and drug screening. In this study we compared global transcriptomes of beating clusters (BCs) microdissected from differentiating human iPS cells and embryonic stem (ES) cells. Hierarchical clustering and principal component analysis revealed that iPS-BCs and ES-BCs cluster together, are similarly enriched for cardiospecific genes and differ in expression of only 1.9% of present transcripts. Similarly, sarcomeric organization, electrophysiological properties and calcium handling of iPS-CMs were indistinguishable from those of ES-CMs. Gene ontology analysis revealed that among 204 genes that were upregulated in iPS-BCs vs ES-BCs the processes related to extracellular matrix, cell adhesion and tissue development were overrepresented. Interestingly, 47 of 106 genes that were upregulated in undifferentiated iPS vs ES cells remained enriched in iPS-BCs vs ES-BCs. Most of these genes were found to be highly expressed in fibroblasts used for reprogramming and 34% overlapped with the recently reported iPS cell-enriched genes. These data suggest that iPS-BCs are transcriptionally highly similar to ES-BCs. However, iPS-BCs appear to share some somatic cell signature with undifferentiated iPS cells. Thus, iPS-BCs may not be perfectly identical to ES-BCs. These minor differences in the expression profiles may occur due to differential cellular composition of iPS-BCs and ES-BCs, due to retention of some genetic profile of somatic cells in differentiated iPS cell-derivatives, or both.