Derivation of hypermethylated pluripotent embryonic stem cells with high potency.
Derivation of hypermethylated pluripotent embryonic stem cells with high potency.
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高效高甲基化多能胚胎干细胞的衍生
DOI：
10.1038/cr.2017.134
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发表时间：
2018-01
期刊：
影响因子：
44.1
通讯作者：
Surani MA
中科院分区：
文献类型：
--
作者：
Bao S;Tang WW;Wu B;Kim S;Li J;Li L;Kobayashi T;Lee C;Chen Y;Wei M;Li S;Dietmann S;Tang F;Li X;Surani MA
幼稚低甲基化胚胎多能干细胞（ESCs）在发育上与囊胚着床前外胚层最接近，除了嵌合胚胎的胚胎外胚层组织外，具有向所有胚胎组织和种系发育的潜力。相比之下，类似于植入后外胚层的外胚层干细胞（EpiSCs）相对来说甲基化程度更高，嵌合的潜力有限。在这里，我们首次揭示了先进的多能干细胞（ASCs），它们在发育上超越了内层细胞群中的多能细胞，但比EpiSCs具有更高的效力。因此，在嵌合体中，单个ASC对胎儿、种系、卵黄囊和胎盘迷宫都有非常有效的贡献。由于ASCs发育较晚，因此不参与滋养层的形成。在含有激活素a和碱性成纤维细胞生长因子的化学培养基中，分两步从囊胚中获得ASCs，然后在含有ActA、BMP4、CHIR99021和白血病抑制因子的ABCL培养基中培养。值得注意的是，ASCs表现出独特的转录组，既表达幼稚多能基因，也表达中胚层体细胞基因；Eomes, Eras, Tdgf1, Evx1, hand1， Wnt5a和不同的重复元素。将已建立的esc转换为ASCs也是可以实现的。重要的是，与囊胚和初始ESCs的低甲基化内细胞群相比，ASCs表现出稳定的高甲基化表观基因组和大部分完整的印迹。ASCs的特性表明它们代表了介于多能性初始状态和启动状态之间的中间细胞状态。
Naive hypomethylated embryonic pluripotent stem cells (ESCs) are developmentally closest to the preimplantation epiblast of blastocysts, with the potential to contribute to all embryonic tissues and the germline, excepting the extra-embryonic tissues in chimeric embryos. By contrast, epiblast stem cells (EpiSCs) resembling postimplantation epiblast are relatively more methylated and show a limited potential for chimerism. Here, for the first time, we reveal advanced pluripotent stem cells (ASCs), which are developmentally beyond the pluripotent cells in the inner cell mass but with higher potency than EpiSCs. Accordingly, a single ASC contributes very efficiently to the fetus, germline, yolk sac and the placental labyrinth in chimeras. Since they are developmentally more advanced, ASCs do not contribute to the trophoblast. ASCs were derived from blastocysts in two steps in a chemically defined medium supplemented with Activin A and basic fibroblast growth factor, followed by culturing in ABCL medium containing ActA, BMP4, CHIR99021 and leukemia inhibitory factor. Notably, ASCs exhibit a distinct transcriptome with the expression of both naive pluripotency genes, as well as mesodermal somatic genes; Eomes, Eras, Tdgf1, Evx1, hand1, Wnt5a and distinct repetitive elements. Conversion of established ESCs to ASCs is also achievable. Importantly, ASCs exhibit a stable hypermethylated epigenome and mostly intact imprints as compared to the hypomethylated inner cell mass of blastocysts and naive ESCs. Properties of ASCs suggest that they represent cells at an intermediate cellular state between the naive and primed states of pluripotency.
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影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
16.8
作者：
Leitch, Harry G.;McEwen, Kirsten R.;Turp, Aleksandra;Encheva, Vesela;Carroll, Tom;Grabole, Nils;Mansfield, William;Nashun, Buhe;Knezovich, Jaysen G.;Smith, Austin;Surani, M. Azim;Hajkova, Petra
通讯作者：
Hajkova, Petra
DOI：
10.1126/science.aag1927
发表时间：
2017-02-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choi YJ;Lin CP;Risso D;Chen S;Kim TA;Tan MH;Li JB;Wu Y;Chen C;Xuan Z;Macfarlan T;Peng W;Lloyd KC;Kim SY;Speed TP;He L
通讯作者：
He L
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
8.8
作者：
Huang, Yali;Osorno, Rodrigo;Wilson, Valerie
通讯作者：
Wilson, Valerie