Parallel bimodal single-cell sequencing of transcriptome and chromatin accessibility

• DOI: 10.1101/gr.257840.119
• Publication Date: 2020-07-22T20:24:36Z
• Authors: Qiao Rui Xing; Chadi A El Farran; Ying Ying Zeng; Yao Yi; Tushar Warrier; Pradeep Gautam; James J. Collins; Jian Xu; Peter Dröge; Cheng-Gee Koh; Hu Li; Li-Feng Zhang; Yuin-Han Loh
• Keywords: Erythroblasts; Transcription Factor; Animal Ecology and Physiology; Molecular Plant Physiology; Method; Cell Line; Epigenesis, Genetic; Mice; 03 medical and health sciences; Animals; Humans; Gene Regulatory Networks; Regulatory Elements, Transcriptional; Cells, Cultured; Embryonic Stem Cells; 0303 health sciences; Cis Regulatory Element; Gene Expression Profiling; :Biological sciences [Science]; Cell Differentiation; Chromatin; 3. Good health; Single-Cell Analysis; Transcriptome; Transcription Factors

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 cis-regulatory elements and target genes unique to each state, and constructed interactome and transcription factor (TF)–centered upstream regulatory networks for various cell states.