Parallel bimodal single-cell sequencing of transcriptome and chromatin accessibility
- Qiao Rui Xing1,2,11,
- Chadi A El Farran1,3,11,
- Ying Ying Zeng1,2,
- Yao Yi1,3,
- Tushar Warrier1,3,
- Pradeep Gautam1,3,
- James J. Collins4,5,6,
- Jian Xu3,7,
- Peter Dröge2,
- Cheng-Gee Koh2,
- Hu Li8,
- Li-Feng Zhang2 and
- Yuin-Han Loh1,3,9,10
- 1Epigenetics and Cell Fates Laboratory, Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore;
- 2School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore;
- 3Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore;
- 4Institute for Medical Engineering and Science, Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
- 5Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
- 6Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA;
- 7Department of Plant Systems Physiology, Institute for Water and Wetland Research, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands;
- 8Center for Individualized Medicine, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA;
- 9NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 119077, Singapore;
- 10Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
-
↵11 These authors contributed equally to this work.
Abstract
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.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.257840.119.
-
Freely available online through the Genome Research Open Access option.
- Received October 2, 2019.
- Accepted June 25, 2020.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
