Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency.
Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency.
复制标题
DOI：
10.1016/j.stem.2020.11.005
复制
发表时间：
2021-03-04
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：
Kinoshita M;Barber M;Mansfield W;Cui Y;Spindlow D;Stirparo GG;Dietmann S;Nichols J;Smith A
多能细胞在胚泡中作为幼稚的创始者群体出现，获得生殖系和索马形成的能力，然后经历谱系启动。小鼠胚胎干细胞（ESC）和外胚层来源的干细胞（EpiSC）分别代表多能性的初始幼稚期和最终致敏期。在这里，我们调查的中间形成阶段。使用最小的暴露规格线索，我们从形成的小鼠上胚层获得干细胞。与ESC或EpiSC不同，形成性干细胞（FS）直接响应生殖细胞诱导。它们在嵌合体中定殖于体细胞组织和生殖细胞。全转录组分析显示与原肠胚形成前形成的上胚层相似。信号反应性和染色质可及性特征反映谱系获能。此外，FS细胞显示出不同的转录因子依赖性，主要依赖于Otx2。最后，应用于人幼稚细胞或胚胎的FS细胞培养条件支持类似干细胞的扩增，这与哺乳动物多能性轨迹上的保守分期站一致。从原肠胚形成前的上胚层衍生小鼠形成性多能干细胞形成性干细胞能够进行生殖系诱导形成性干细胞可以促进嵌合体使用与小鼠相似的培养条件衍生的候选人FS细胞已经提出了三个多能性阶段：幼稚、形成和引发。Kinoshita及其同事通过在低生长因子刺激条件下培养小鼠外胚层，获得了具有形成多能性特性的干细胞。应用于人类胚胎导致了类似干细胞的繁殖。
Pluripotent cells emerge as a naive founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs) represent the initial naive and final primed phases of pluripotency, respectively. Here, we investigate the intermediate formative stage. Using minimal exposure to specification cues, we derive stem cells from formative mouse epiblast. Unlike ESCs or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonize somatic tissues and germline in chimeras. Whole-transcriptome analyses show similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells show distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naive cells or embryos support expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency. Derivation of mouse formative pluripotent stem cells from pre-gastrulation epiblast Formative stem cells are competent for germline induction Formative stem cells can contribute to chimeras Candidate human FS cells derived using similar culture conditions to mouse Three stages of pluripotency have been proposed: naive, formative, and primed. Kinoshita and colleagues derived stem cells with properties anticipated for formative pluripotency by culturing mouse epiblast under conditions of low growth factor stimulation. Application to human embryos resulted in propagation of similar stem cells.
登录
查看更多内容
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：
5.9
作者：
D'Aniello C;Habibi E;Cermola F;Paris D;Russo F;Fiorenzano A;Di Napoli G;Melck DJ;Cobellis G;Angelini C;Fico A;Blelloch R;Motta A;Stunnenberg HG;De Cesare D;Patriarca EJ;Minchiotti G
通讯作者：
Minchiotti G
影响因子：
64.8
作者：
Brennan, J;Lu, CC;Robertson, EJ
通讯作者：
Robertson, EJ
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：
Cheng, Shangli;Pei, Yu;Deng, Qiaolin
通讯作者：
Deng, Qiaolin