Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research.
Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research.
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DOI：
10.1186/s11689-016-9155-8
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发表时间：
2016
影响因子：
4.9
通讯作者：
Constantino JN
中科院分区：
文献类型：
--
作者：
Dandulakis MG;Meganathan K;Kroll KL;Bonni A;Constantino JN
诱导多能干细胞(IPSCs)允许研究人员通过对非侵入性提取的体细胞进行重新编程来定制患者来源的细胞系。这些细胞系有可能忠实地代表个体的遗传背景；因此，在没有活着患者的可用人脑组织的情况下，这些模型相对于其他神经发育疾病模型具有显著的优势。当使用人类诱导多能干细胞(HiPSCs)来建立X连锁发育障碍或遗传性疾病的模型时(例如，自闭症谱系障碍)，在建立细胞模型的有效性时，X染色体失活(XCI)的过程和状态是非常复杂的。在现有文献中，在hPSCs的衍生和维持以及其向神经元分化的过程中，存在着关于XCI状态的主要空白和不一致之处。在这里，我们简要描述这个问题的重要性，回顾现有文献的发现和不一致之处，勾勒出在克隆群体中指定XCI状态的选项，并为未来的研究提出建议。
Induced pluripotent stem cells (iPSCs) allow researchers to make customized patient-derived cell lines by reprogramming noninvasively retrieved somatic cells. These cell lines have the potential to faithfully represent an individual’s genetic background; therefore, in the absence of available human brain tissue from a living patient, these models have a significant advantage relative to other models of neurodevelopmental disease. When using human induced pluripotent stem cells (hiPSCs) to model X-linked developmental disorders or inherited conditions that undergo sex-specific modulation of penetrance (e.g., autism spectrum disorders), there are significant complexities in the course and status of X chromosome inactivation (XCI) that are crucial to consider in establishing the validity of cellular models. There are major gaps and inconsistencies in the existing literature regarding XCI status during the derivation and maintenance of hiPSCs and their differentiation into neurons. Here, we briefly describe the importance of the problem, review the findings and inconsistencies of the existing literature, delineate options for specifying XCI status in clonal populations, and develop recommendations for future studies.