Epigenetics and Cell Fates Laboratory, Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore.
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Genome Res. 2020 Jul;30(7):1027-1039. doi: 10.1101/gr.257840.119. Epub 2020 Jul 22.
Joint profiling of transcriptome and chromatin accessibility within single cells allows for the deconstruction of the complex relationship between transcriptional states and upstream regulatory programs determining different cell fates. Here, we developed an automated method with high sensitivity, assay for single-cell transcriptome and accessibility regions (ASTAR-seq), for simultaneous measurement of whole-cell transcriptome and chromatin accessibility within the same single cell. To show the utility of ASTAR-seq, we profiled 384 mESCs under naive and primed pluripotent states as well as a two-cell like state, 424 human cells of various lineage origins (BJ, K562, JK1, and Jurkat), and 480 primary cord blood cells undergoing erythroblast differentiation. With the joint profiles, we configured the transcriptional and chromatin accessibility landscapes of discrete cell states, uncovered linked sets of -regulatory elements and target genes unique to each state, and constructed interactome and transcription factor (TF)-centered upstream regulatory networks for various cell states.
单细胞内转录组和染色质可及性的联合分析可以深入了解转录状态与决定不同细胞命运的上游调控程序之间的复杂关系。在这里，我们开发了一种具有高灵敏度的自动化方法，用于单细胞转录组和可及性区域的分析（ASTAR-seq），可在同一单细胞内同时测量全细胞转录组和染色质可及性。为了展示 ASTAR-seq 的实用性，我们对处于原始态和诱导多能态以及类似二细胞状态的 384 个 mESCs、来自不同谱系的 424 个人类细胞（BJ、K562、JK1 和 Jurkat）以及正在进行红细胞分化的 480 个原脐带血细胞进行了分析。通过联合分析，我们构建了离散细胞状态的转录组和染色质可及性图谱，揭示了与每个状态相关的独特的调控元件和靶基因的关联集，并构建了各种细胞状态的互作网络和以转录因子为中心的上游调控网络。
