Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.
Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.
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DOI：
10.1002/stem.1675
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发表时间：
2014-06
期刊：
影响因子：
5.2
通讯作者：
Kim, Yong
中科院分区：
文献类型：
--
作者：
Kim, Jeffrey J.;Khalid, Omar;Namazi, AmirHosien;Tu, Thanh G.;Elie, Omid;Lee, Connie;Kim, Yong
关键词：
定义自我更新多能胚胎干细胞（ESC）的分子标记已通过未分化细胞和分化细胞之间的相对比较来确定。大多数分析都是在特定的分化条件下进行的，这些条件可能会呈现出与其他条件显著不同的分子变化。因此，目前尚不清楚是否存在定义未分化hESC的真正共识标志物。为了鉴定一组在hESC分化过程中一致改变的关键基因，无论分化条件如何，我们对未分化的hESC（H1和H9）和分化的EB进行了微阵列分析，并使用公开可用的表达阵列数据集验证了我们的结果。我们构建了共识模块加权基因相关分析（WGCNA），并发现了新的标记，始终存在于未分化的hESC在各种分化条件下。我们已经验证了分化后的顶级标志物（下调：LCK，KLKB 1和SLC 7A 3;上调：RhoJ，Zeb 2和Adam 12）。通过使用LCK抑制剂或用siLCK进行基因沉默，LCK在hESC自我更新中的功能验证分析导致未分化特征的丧失-形态学改变、碱性磷酸酶活性降低和多能性基因表达，证明LCK在hESC自我更新中的潜在功能作用。我们已经将hESC标记指定为基因组中的交互网络，确定可能的交互伙伴并显示新标记如何相互关联。此外，将这些数据集与来自iPSC的可用数据集进行比较，揭示了这些新鉴定的标志物的水平与iPSC的建立相关，这可能意味着这些标志物在获得细胞潜能中的潜在作用。
Molecular markers defining self-renewing pluripotent embryonic stem cells (ESCs) have been identified by relative comparisons between undifferentiated and differentiated cells. Most of analysis has been done under a specific differentiation condition that may present significantly different molecular changes over others. Therefore, it is currently unclear if there are true consensus markers defining undifferentiated hESCs. To identify a set of key genes consistently altered during differentiation of hESCs regardless of differentiation conditions we have performed microarray analysis on undifferentiated hESCs (H1 and H9) and differentiated EB’s and validated our results using publicly available expression array data sets. We constructed consensus modules by Weighted Gene Correlation Analysis (WGCNA) and discovered novel markers that are consistently present in undifferentiated hESCs under various differentiation conditions. We have validated top markers (downregulated: LCK, KLKB1 and SLC7A3; upregulated: RhoJ, Zeb2 and Adam12) upon differentiation. Functional validation analysis of LCK in self-renewal of hESCs by using LCK inhibitor or gene silencing with siLCK resulted in a loss of undifferentiation characteristics- morphological change, reduced alkaline phosphatase activity and pluripotency gene expression, demonstrating a potential functional role of LCK in self-renewal of hESCs. We have designated hESC markers to interactive networks in the genome, identifying possible interacting partners and showing how new markers relate to each other. Furthermore, comparison of these data sets with available datasets from iPSCs revealed that the level of these newly identified markers were correlated to the establishment of iPSCs, which may imply a potential role of these markers in gaining of cellular potency.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
3.7
作者：
Bhatia S;Pilquil C;Roth-Albin I;Draper JS
通讯作者：
Draper JS
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
10.5
作者：
Lapasset, Laure;Milhavet, Ollivier;Lemaitre, Jean-Marc
通讯作者：
Lemaitre, Jean-Marc
影响因子：
4
作者：
Lowry, William E.
通讯作者：
Lowry, William E.