近日，英国剑桥大学Austin Smith、Masaki Kinoshita等研究人员合作获得具有形成性多能性的小鼠和人类干细胞。2020年12月2日，《细胞—干细胞》杂志在线发表了这项成果。

研究人员表示，多能细胞在囊胚中作为初始群体出现，获得种系和体细胞形成的能力，然后进行谱系启动。小鼠胚胎干细胞（ESC）和表皮细胞衍生的干细胞（EpiSC）分别代表了多能性的最初起始和最终活化阶段。

研究人员测试了中间态的形成性阶段。通过使用最低的分化信号处理，研究人员从形成性小鼠上皮细胞中衍生出干细胞。与ESC或EpiSC不同，形成性干（FS）细胞直接对生殖细胞诱导产生反应。他们在嵌合体中定殖体细胞组织和种系。全转录组分析显示与妊娠前形成性成骨细胞相似。信号响应能力和染色质可及性特征反映了谱系获能。此外，FS细胞显示出独特的转录因子依赖性，并严重依赖于Otx2。

最后，适用于人类初始细胞或胚胎的FS细胞培养条件能够支持类似干细胞的扩增，这与哺乳动物多能性轨迹的保守形成一致。

附：英文原文

Title: Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency

Author: Masaki Kinoshita, Michael Barber, William Mansfield, Yingzhi Cui, Daniel Spindlow, Giuliano Giuseppe Stirparo, Sabine Dietmann, Jennifer Nichols, Austin Smith

Issue&Volume: 2020-12-02

Abstract: 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.

DOI: 10.1016/j.stem.2020.11.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30543-9