Totipotent embryonic stem cells arise in ground-state culture conditions.
Totipotent embryonic stem cells arise in ground-state culture conditions.
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DOI：
10.1016/j.celrep.2013.04.034
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发表时间：
2013-06-27
期刊：
影响因子：
8.8
通讯作者：
Brickman JM
中科院分区：
文献类型：
--
作者：
Morgani SM;Canham MA;Nichols J;Sharov AA;Migueles RP;Ko MS;Brickman JM
胚胎干细胞（ESCs）来源于哺乳动物胚胎，在从全能性（当单个卵裂球可以产生所有谱系时）到多能性（当它们有能力仅产生胚胎谱系时）的过渡期间。用MEK和GSK 3（2i）抑制剂维持的ESC被认为代表胚胎限制的基态。然而，我们观察到异质性表达的胚外内胚层标记六角在2i培养的胚胎，这表明2i阻止前外胚层承诺的发展。同样地，2i ESC培养物是异质的，并且含有引发分化成滋养层和胚外内胚层的Hex阳性部分。单个Hex阳性ESC共表达外胚层和胚外基因，并在嵌合体中贡献于所有谱系。ESC自我更新所必需的细胞因子LIF支持该群体的扩增，但不直接支持Nanog阳性外胚层样ESC。因此，2i和LIF支持与共表达胚胎和胚外决定簇的早期胚胎细胞相当的全能状态。在2i中培养的胚胎在胚外谱系分离之前被阻断在2i中培养的ESC不均匀地表达胚外标记物单个2i ESC分化成胚胎和胚外谱系LIF促进胚外引发的ESC群体的增殖胚胎干细胞（ESC）从植入前胚胎中分离，并且可以对胚胎的所有组织，但不是胚外组织（例如，胎盘）。因此，它们被认为是多能的，而不是全能的。Brickman及其同事现在表明，在MEK和GSK3抑制剂存在下培养的单个ESC（2i）共表达胚胎和胚外标记物，并有助于胚胎和胚外组织（例如，是全能的）。细胞因子LIF在ESC自我更新中的作用是支持这种全能群体。
Embryonic stem cells (ESCs) are derived from mammalian embryos during the transition from totipotency, when individual blastomeres can make all lineages, to pluripotency, when they are competent to make only embryonic lineages. ESCs maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, we observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. Single Hex-positive ESCs coexpressed epiblast and extraembryonic genes and contributed to all lineages in chimeras. The cytokine LIF, necessary for ESC self-renewal, supported the expansion of this population but did not directly support Nanog-positive epiblast-like ESCs. Thus, 2i and LIF support a totipotent state comparable to early embryonic cells that coexpress embryonic and extraembryonic determinants. Embryos cultured in 2i are blocked before extraembryonic lineage segregation ESCs cultured in 2i express extraembryonic markers heterogeneously Single 2i ESCs differentiate into both embryonic and extraembryonic lineages LIF promotes proliferation of extraembryonically primed ESC populations Embryonic stem cells (ESCs) are isolated from preimplantation embryos and can contribute to all tissues of the embryo, but not extraembryonic tissues (e.g., placenta). Therefore, they are considered pluripotent, not totipotent. Brickman and colleagues now show that single ESCs cultured in the presence of MEK and GSK3 inhibitors (2i) coexpress embryonic and extraembryonic markers and contribute to both embryonic and extraembryonic tissues (e.g., are totipotent). A role of the cytokine LIF in ESC self-renewal is to support this totipotent population.
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影响因子：
11.8
作者：
Rugg-Gunn, Peter J.;Cox, Brian J.;Lanner, Fredrik;Sharma, Parveen;Ignatchenko, Vladimir;McDonald, Angela C. H.;Garner, Jodi;Gramolini, Anthony O.;Rossant, Janet;Kislinger, Thomas
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
2.1
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Hayashi, Yohei;Furue, Miho Kusuda;Tanaka, Satoshi;Hirose, Michiko;Wakisaka, Noriko;Danno, Hiroki;Ohnuma, Kiyoshi;Oeda, Shiho;Aihara, Yuko;Shiota, Kunio;Ogura, Atsuo;Ishiura, Shoichi;Asashima, Makoto
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