Transcriptional Heterogeneity in Naive and Primed Human Pluripotent Stem Cells at Single-Cell Resolution
Transcriptional Heterogeneity in Naive and Primed Human Pluripotent Stem Cells at Single-Cell Resolution
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DOI：
10.1016/j.celrep.2018.12.099
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发表时间：
2019-01-22
期刊：
影响因子：
8.8
通讯作者：
Reik, Wolf
中科院分区：
文献类型：
--
作者：
Messmer, Tobias;von Meyenn, Ferdinand;Reik, Wolf
传统的人胚胎干细胞被认为是引发的多能性的，但可以被诱导进入幼稚状态。然而，与幼稚和引发的多能性相关的转录特征仍然没有完全理解。在这里，我们使用单细胞RNA测序来表征这些条件之间的差异。我们观察到，幼稚和引发的群体大多是同质的，没有明确的谱系相关的结构，并确定了一个中间亚群的幼稚细胞与引发样表达。我们发现，幼稚引发的多能性轴是跨物种保存，虽然过渡到引发状态的时间是物种特异性的。我们还鉴定了用于区分人类幼稚和引发多能性的标记物，以及谱系标记物和幼稚细胞独有的表观遗传调节因子之间的强共调节关系。我们的数据提供了有价值的见解，人类多能性的转录景观在细胞和全基因组的分辨率。
Conventional human embryonic stem cells are considered to be primed pluripotent but can be induced to enter a naive state. However, the transcriptional features associated with naive and primed pluripotency are still not fully understood. Here we used single-cell RNA sequencing to characterize the differences between these conditions. We observed that both naive and primed populations were mostly homogeneous with no clear lineage-related structure and identified an intermediate sub-population of naive cells with primed-like expression. We found that the naive-primed pluripotency axis is preserved across species, although the timing of the transition to a primed state is species specific. We also identified markers for distinguishing human naive and primed pluripotency as well as strong coregulatory relationships between lineage markers and epigenetic regulators that were exclusive to naive cells. Our data provide valuable insights into the transcriptional landscape of human pluripotency at a cellular and genome-wide resolution.