Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming.
Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming.
复制标题
DOI：
10.1038/ncomms12354
复制
发表时间：
2016-08-10
影响因子：
16.6
通讯作者：
Fisher AG
中科院分区：
文献类型：
--
作者：
Cantone I;Bagci H;Dormann D;Dharmalingam G;Nesterova T;Brockdorff N;Rougeulle C;Vallot C;Heard E;Chaligne R;Merkenschlager M;Fisher AG
消除表观遗传记忆是将体细胞转化为多能性所必需的。失活X染色体（Xi）的重新激活已被用于模拟小鼠的表观遗传重编程，但人类研究受到Xi表观遗传不稳定性和难以追踪部分重编程iPSC的阻碍。在这里，我们使用细胞融合来检查最早的事件中的重编程诱导的Xi重新激活人类女性成纤维细胞。我们发现，快速和广泛的损失Xi相关的H3 K27 me 3和XIST发生在融合细胞和之前的双等位基因表达的选择Xi基因的许多异核体（30-50%）。在细胞分裂后，RNA-FISH和RNA-seq分析证实Xi再活化仍然是部分的，并且人类多能特异性XACT转录物的诱导是罕见的（1%）。这些数据有效地分离了重编程诱导的Xi重新激活中的有丝分裂前和有丝分裂后事件，并揭示了重新激活人类Xi染色体上的基因所需的表观遗传变化的复杂层次。 失活X染色体（Xi）的重新激活模拟了小鼠中的表观遗传重编程。在这里，通过使用人类女性成纤维细胞和小鼠胚胎干细胞之间的细胞融合，作者展示了重新激活人类Xi染色体上的基因所需的表观遗传变化的复杂层次。
Erasure of epigenetic memory is required to convert somatic cells towards pluripotency. Reactivation of the inactive X chromosome (Xi) has been used to model epigenetic reprogramming in mouse, but human studies are hampered by Xi epigenetic instability and difficulties in tracking partially reprogrammed iPSCs. Here we use cell fusion to examine the earliest events in the reprogramming-induced Xi reactivation of human female fibroblasts. We show that a rapid and widespread loss of Xi-associated H3K27me3 and XIST occurs in fused cells and precedes the bi-allelic expression of selected Xi-genes by many heterokaryons (30–50%). After cell division, RNA-FISH and RNA-seq analyses confirm that Xi reactivation remains partial and that induction of human pluripotency-specific XACT transcripts is rare (1%). These data effectively separate pre- and post-mitotic events in reprogramming-induced Xi reactivation and reveal a complex hierarchy of epigenetic changes that are required to reactivate the genes on the human Xi chromosome. Reactivation of the inactive X chromosome (Xi) has modelled epigenetic reprogramming in mouse. Here, by using cell fusion between human female fibroblasts and mouse embryonic stem cells, the authors show a complex hierarchy of epigenetic changes that are required to reactivate the genes on the human Xi chromosome.
影响因子：
3.7
作者：
Thorogood NP;Brown CJ
通讯作者：
Brown CJ