Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium.
Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium.
复制标题
来自祖细胞生物学联盟的不同诱导多能干细胞的综合基因组分析。
DOI：
10.1016/j.stemcr.2016.05.006
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发表时间：
2016-07-12
影响因子：
5.9
通讯作者：
Lutzko C
中科院分区：
文献类型：
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作者：
Salomonis N;Dexheimer PJ;Omberg L;Schroll R;Bush S;Huo J;Schriml L;Ho Sui S;Keddache M;Mayhew C;Shanmukhappa SK;Wells J;Daily K;Hubler S;Wang Y;Zambidis E;Margolin A;Hide W;Hatzopoulos AK;Malik P;Cancelas JA;Aronow BJ;Lutzko C
需要对来自多种重编程技术、体细胞来源和供体的不同诱导多能干细胞（iPSC）进行严格表征，以了解变异性和下游潜力的潜在来源。为了实现这一目标，祖细胞生物学联盟对来自10个实验室的58个iPSC进行了全面的实验和基因组分析，这些实验室使用各种重编程基因、载体和细胞产生iPSC。相关的全球分子表征研究确定了关键发育和致癌调控因子之间的基因表达、DNA甲基化和/或拷贝数变异的功能信息相关性，这些相关性是供体、性别、细胞系稳定性、重编程技术和细胞来源的结果。此外，PSC中的X染色体失活在分化后畸胎瘤谱系染色和调节剂表达中产生高度相关的差异。所有的实验结果，以及来自这些分析的原始、处理和元数据，包括强大的工具，都可以从一个新的在线门户网站https://www.synapse.org交互式访问，作为干细胞社区的可重复使用的资源。在重编程过程中发生复发性CNV，影响癌基因和肿瘤抑制因子DNA甲基化受iPSC PSC中来源细胞的影响X染色体失活影响谱系分化结果来自不同实验室、来源供体、重编程方法和培养条件的诱导多能干细胞（iPSC）之间存在固有差异。为了仔细评估这些差异，Lutzko和来自祖细胞生物学联盟的同事们描述了用不同方法产生的数十个iPSC，以确定方法学和供体特异性差异。
The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental and genomic analyses of 58 iPSC from ten laboratories generated using a variety of reprogramming genes, vectors, and cells. Associated global molecular characterization studies identified functionally informative correlations in gene expression, DNA methylation, and/or copy-number variation among key developmental and oncogenic regulators as a result of donor, sex, line stability, reprogramming technology, and cell of origin. Furthermore, X-chromosome inactivation in PSC produced highly correlated differences in teratoma-lineage staining and regulator expression upon differentiation. All experimental results, and raw, processed, and metadata from these analyses, including powerful tools, are interactively accessible from a new online portal at https://www.synapse.org to serve as a reusable resource for the stem cell community. Comprehensive portal for diverse iPSC, protocols, metadata, and genomic assays Recurrent CNV occur during reprogramming, impact oncogenes and tumor suppressors DNA methylation is influenced by cell of origin in iPSC PSC X-chromosome inactivation impacts lineage differentiation outcomes Inherent differences exist among induced pluripotent stem cells (iPSC) from different laboratories, donor of origin, reprogramming methods, and culturing conditions. To carefully evaluate these differences, Lutzko and colleagues from the Progenitor Cell Biology Consortium characterize dozens of iPSC generated with diverse methods to identify methodological and donor-specific differences.