A Molecular Roadmap of the Phased Progression of Pluripotency

Pluripotency is highly dynamic and progresses through a continuum of pluripotent stem cell states. The two states that bookend the pluripotency continuum, naïve and primed, are well characterized, but our understanding of the intermediate states and the transitions between them remain incomplete. To address this gap in knowledge, using a previously validated system to induce naive mouse embryonic stem cells (ESCs) to post-implantation pre-grastrulating epiblast-like cells (EpiLCs), we generated comprehensive high-temporal-resolution maps of the proteome, phosphoproteome, transcriptome, and epigenome of ESCs transitioning from naïve to primed pluripotency. Our data provide a comprehensive molecular description of the phased progression of pluripotency and a foundation for investigating mechanisms that regulate pluripotent state transitions. RNA-Seq and ChIP-Seq experiments at various time-points during the 72-hour ESC to EpiLC transition

多能性（pluripotency）具有高度动态特性，其发生发展贯穿多能干细胞状态的连续谱系。构成该多能性连续谱系两端的初始态（naïve）与始发态（primed）已得到充分表征，但我们对中间状态及其间转换过程的认知仍存在缺口。为填补这一认知空白，本研究借助已验证的实验体系，将初始态小鼠胚胎干细胞（embryonic stem cells, ESCs）诱导为着床后原肠胚形成前的上胚层样细胞（epiblast-like cells, EpiLCs），并绘制了从初始态向始发态多能性转换的胚胎干细胞的蛋白质组、磷酸化蛋白质组、转录组及表观基因组的高时间分辨率全景图谱。本研究数据为多能性的阶段性演进提供了全面的分子层面描述，同时为探究调控多能状态转换的机制奠定了研究基础。在72小时ESC向EpiLC转换过程中，多个时间点下的RNA测序（RNA-Seq）与染色质免疫沉淀测序（ChIP-Seq）实验