Human naive epiblast cells possess unrestricted lineage potential.
Human naive epiblast cells possess unrestricted lineage potential.
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DOI：
10.1016/j.stem.2021.02.025
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发表时间：
2021-06-03
期刊：
影响因子：
23.9
通讯作者：
Smith A
中科院分区：
文献类型：
--
作者：
Guo G;Stirparo GG;Strawbridge SE;Spindlow D;Yang J;Clarke J;Dattani A;Yanagida A;Li MA;Myers S;Özel BN;Nichols J;Smith A
经典的胚胎学实验已经确定，早期小鼠胚胎通过连续谱系分叉发育。第一个分离的谱系是滋养外胚层，对胚泡形成至关重要。因此，小鼠幼稚上胚层和衍生的胚胎干细胞被限制产生滋养外胚层。在这里，我们表明，相反，人类幼稚胚胎干细胞很容易使胚泡滋养外胚层和后代滋养层细胞类型。通过抑制ERK/丝裂原活化蛋白激酶（MAPK）和Nodal信号传导，快速有效地诱导滋养外胚层。与人类胚胎的转录组比较证实了滋养外胚层的直接形成，随后分化为合胞体滋养层、细胞滋养层和下游滋养层干细胞。在多能性进展期间，谱系电位从滋养外胚层切换到羊膜。活细胞追踪显示，人类胚泡中的上胚层细胞也能够产生滋养外胚层。因此，发育规范与谱系限制相结合的范式并不适用于人类。相反，上胚层的可塑性和胚泡再生的潜力被保留，直到植入。人类幼稚多能干细胞直接形成囊胚滋养外胚层与小鼠不同，人类幼稚上胚层再生滋养外胚层ERK和Nodal的抑制驱动滋养外胚层分化在多能性进展期间从滋养外胚层到羊膜的潜能变化人类多能干细胞（hPSC）存在于幼稚或启动状态，但尚不清楚这些是否对应于不同的发育潜能。在这里，Guo et al.显示幼稚hPSC分化成滋养外胚层，胎盘的建立者组织，而引发的hPSC已经失去了这种潜力，而是形成羊膜。
Classic embryological experiments have established that the early mouse embryo develops via sequential lineage bifurcations. The first segregated lineage is the trophectoderm, essential for blastocyst formation. Mouse naive epiblast and derivative embryonic stem cells are restricted accordingly from producing trophectoderm. Here we show, in contrast, that human naive embryonic stem cells readily make blastocyst trophectoderm and descendant trophoblast cell types. Trophectoderm was induced rapidly and efficiently by inhibition of ERK/mitogen-activated protein kinase (MAPK) and Nodal signaling. Transcriptome comparison with the human embryo substantiated direct formation of trophectoderm with subsequent differentiation into syncytiotrophoblast, cytotrophoblast, and downstream trophoblast stem cells. During pluripotency progression lineage potential switches from trophectoderm to amnion. Live-cell tracking revealed that epiblast cells in the human blastocyst are also able to produce trophectoderm. Thus, the paradigm of developmental specification coupled to lineage restriction does not apply to humans. Instead, epiblast plasticity and the potential for blastocyst regeneration are retained until implantation. Human naive pluripotent stem cells form blastocyst trophectoderm directly Unlike in mouse, human naive epiblast regenerates trophectoderm Inhibition of ERK and Nodal drives trophectoderm differentiation Potency changes from trophectoderm to amnion during pluripotency progression Human pluripotent stem cells (hPSCs) exist in naive or primed states, but it has been unclear whether these correspond to distinct developmental potencies. Here, Guo et al. show that naive hPSCs differentiate into trophectoderm, the founder tissue of the placenta, whereas primed hPSCs have lost this potential and instead form the amnion.
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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
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1242/dev.167833
发表时间：
2018-11-09
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Boroviak T;Stirparo GG;Dietmann S;Hernando-Herraez I;Mohammed H;Reik W;Smith A;Sasaki E;Nichols J;Bertone P
通讯作者：
Bertone P
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
7.7
作者：
Dong, Chen;Beltcheva, Mariana;Theunissen, Thorold W.
通讯作者：
Theunissen, Thorold W.