Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.
Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.
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DOI：
10.1016/j.stem.2016.10.006
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发表时间：
2017-01-05
期刊：
影响因子：
23.9
通讯作者：
Plath, Kathrin
中科院分区：
文献类型：
--
作者：
Sahakyan, Anna;Kim, Rachel;Chronis, Constantinos;Sabri, Shan;Bonora, Giancarlo;Theunissen, Thorold W.;Kuoy, Edward;Langerman, Justin;Clark, Amander T.;Jaenisch, Rudolf;Plath, Kathrin
幼稚的人类胚胎干细胞(HESCs)可以来自预置的hESCs，也可以直接来自胚泡，但它们的X染色体状态仍未解决。在这里，我们展示了在幼稚的培养条件下，启动的hESCs的非活性X染色体(XI)被重新激活。与胚泡细胞类似，所产生的幼稚细胞含有两条活跃的X染色体，具有XIST表达和全染色体转录抑制，并在分化时启动XIST介导的X-失活。幼稚状态(分化)的建立和退出都是通过XIST阴性的Xaxa中间体进行的。总之，这些发现确定了一个细胞培养系统，用于从功能上探索人类早期发育中的两个X染色体剂量补偿过程：X抑制和X失活。然而，幼稚的人类胚胎干细胞和胚胎细胞之间在单等位XIST表达和非随机X失活方面的差异突出了进一步培养改进的必要性。随着天真状态重置在启动的hESCs中看到的xi异常，它可能会提供更适合下游应用的细胞。
Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. Here, we show that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment of and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. However, remaining differences between naïve hESCs and embryonic cells related to monoallelic XIST expression and non-random X-inactivation highlight the need for further culture improvement. As the naïve state reset Xi abnormalities seen in primed hESCs it may provide cells better suited for downstream applications.
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影响因子：
64.5
作者：
Takashima Y;Guo G;Loos R;Nichols J;Ficz G;Krueger F;Oxley D;Santos F;Clarke J;Mansfield W;Reik W;Bertone P;Smith A
通讯作者：
Smith A
影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
23.9
作者：
Pastor WA;Chen D;Liu W;Kim R;Sahakyan A;Lukianchikov A;Plath K;Jacobsen SE;Clark AT
通讯作者：
Clark AT
影响因子：
23.9
作者：
Tchieu J;Kuoy E;Chin MH;Trinh H;Patterson M;Sherman SP;Aimiuwu O;Lindgren A;Hakimian S;Zack JA;Clark AT;Pyle AD;Lowry WE;Plath K
通讯作者：
Plath K
影响因子：
64.5
作者：
Sahakyan A;Plath K
通讯作者：
Plath K