High-resolution chromosomal microarray analysis of early-stage human embryonic stem cells reveals an association between X chromosome instability and skewed X inactivation.
High-resolution chromosomal microarray analysis of early-stage human embryonic stem cells reveals an association between X chromosome instability and skewed X inactivation.
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早期人类胚胎干细胞的高分辨率染色体微阵列分析揭示了 X 染色体不稳定性与倾斜 X 失活之间的关联
DOI：
10.1186/2045-3701-4-74
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发表时间：
2014
影响因子：
7.5
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Luo Y;Li J;Zhu D;Fan Y;Li S;Sun X
X 染色体失活 (XCI) 是一种剂量补偿机制，通过随机过程沉默每个雌性细胞中一条 X 染色体上的大多数基因。偏斜的 XCI 与许多疾病相关，但导致其的机制仍不清楚。源自囊胚期胚胎内细胞团 (ICM) 的人胚胎干细胞 (hESC) 为了解 XCI 的启动和维持提供了一个极好的模型系统。在这里，我们从劣质胚胎中衍生出具有随机或倾斜 XCI 模式的 hESC 系，并研究了这两组 hESC 系早期传代时的全基因组拷贝数变异 (CNV) 和杂合性丢失 (LOH) 模式。结果发现，倾斜组 X 染色体上 CNV 的平均大小是随机组的两倍。此外，倾斜组的 LOH 区域覆盖了 XIST 或 XACT 的基因位点，它们是人类多能干细胞中 XCI 的主要长非编码 RNA (lncRNA) 效应子。总之，我们的工作建立了一种实验上易于处理的 hESC 模型，用于研究偏斜 XCI，并揭示了 X 染色体不稳定性与偏斜 XCI 之间的关联。本文的在线版本 (doi:10.1186/2045-3701-4-74) 包含补充材料，可供授权用户使用。
X chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell via a random process. Skewed XCI is relevant to many diseases, but the mechanism leading to it remains unclear. Human embryonic stem cells (hESCs) derived from the inner cell mass (ICM) of blastocyst-stage embryos have provided an excellent model system for understanding XCI initiation and maintenance. Here, we derived hESC lines with random or skewed XCI patterns from poor-quality embryos and investigated the genome-wide copy number variation (CNV) and loss of heterozygosity (LOH) patterns at the early passages of these two groups of hESC lines. It was found that the average size of CNVs on the X chromosomes in the skewed group is twice as much as that in the random group. Moreover, the LOH regions of the skewed group covered the gene locus of either XIST or XACT, which are master long non-coding RNA (lncRNA) effectors of XCI in human pluripotent stem cells. In conclusion, our work has established an experimentally tractable hESC model for study of skewed XCI and revealed an association between X chromosome instability and skewed XCI. The online version of this article (doi:10.1186/2045-3701-4-74) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
Hoffman, LM;Hall, L;Carpenter, MK
通讯作者：
Carpenter, MK
影响因子：
4
作者：
Kristiansen, M;Langerod, A;Orstavik, KH
通讯作者：
Orstavik, KH
影响因子：
14.9
作者：
Dhara, SK;Benvenisty, N
通讯作者：
Benvenisty, N
影响因子：
--
作者：
Luo Y;Zhu D
通讯作者：
Zhu D
影响因子：
3.7
作者：
Dvash, Tamar;Fan, Guoping
通讯作者：
Fan, Guoping