Genetically matched human iPS cells reveal that propensity for cartilage and bone differentiation differs with clones, not cell type of origin.
Genetically matched human iPS cells reveal that propensity for cartilage and bone differentiation differs with clones, not cell type of origin.
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基因匹配的人类 iPS 细胞表明，软骨和骨分化的倾向因克隆而异，而非细胞来源类型的不同。
DOI：
10.1371/journal.pone.0053771
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Toguchida J
中科院分区：
文献类型：
--
作者：
Nasu A;Ikeya M;Yamamoto T;Watanabe A;Jin Y;Matsumoto Y;Hayakawa K;Amano N;Sato S;Osafune K;Aoyama T;Nakamura T;Kato T;Toguchida J
对于使用诱导多能干细胞（iPSC）技术的再生疗法，应基于可及性和重编程效率来选择待重编程的细胞来源类型。一些研究报告说，iPSC表现出分化成其原始细胞谱系的偏好，而另一些则没有。因此，需要澄清最适合作为iPSC来源的细胞类型。使用同一供体的骨髓基质细胞（BMSC）和真皮成纤维细胞（DF）产生来自不同来源的遗传匹配的人iPSC，并分析每个克隆的全局基因表达谱、DNA甲基化状态和成软骨和成骨谱系的分化特性。虽然DNA甲基化的全基因组分析表明iPSC中存在组织记忆，但在BMSC和DF中差异表达的基因在我们真正的iPSC中同样沉默。在细胞自主分化和诱导分化后，每个iPSC克隆表现出各种分化特性，这与细胞来源无关。重编程过程可以消除DF和BMSC之间的差异，至少对于软骨和成骨分化。本研究中建立的合格和遗传匹配的人类iPSC克隆集是进一步研究克隆差异的宝贵资源。
For regenerative therapy using induced pluripotent stem cell (iPSC) technology, cell type of origin to be reprogrammed should be chosen based on accessibility and reprogramming efficiency. Some studies report that iPSCs exhibited a preference for differentiation into their original cell lineages, while others did not. Therefore, the type of cell which is most appropriate as a source for iPSCs needs to be clarified. Genetically matched human iPSCs from different origins were generated using bone marrow stromal cells (BMSCs) and dermal fibroblasts (DFs) of the same donor, and global gene expression profile, DNA methylation status, and differentiation properties into the chondrogenic and osteogenic lineage of each clone were analyzed. Although genome-wide profiling of DNA methylation suggested tissue memory in iPSCs, genes expressed differentially in BMSCs and DFs were equally silenced in our bona fide iPSCs. After cell-autonomous and induced differentiation, each iPSC clone exhibited various differentiation properties, which did not correlate with cell-of-origin. The reprogramming process may remove the difference between DFs and BMSCs at least for chondrogenic and osteogenic differentiation. Qualified and genetically matched human iPSC clone sets established in this study are valuable resources for further basic study of clonal differences.
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