@article{5a12e00ae91d4f41a6c7aff00d1e3dab,
title = "Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin",
abstract = "Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events leading to cell fate commitment. Here we developed simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq), a highly scalable approach for measurement of chromatin accessibility and gene expression in the same single cell, applicable to different tissues. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identify cis-regulatory interactions and define domains of regulatory chromatin (DORCs) that significantly overlap with super-enhancers. During lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for lineage commitment. We computationally infer chromatin potential as a quantitative measure of chromatin lineage-priming and use it to predict cell fate outcomes. SHARE-seq is an extensible platform to study regulatory circuitry across diverse cells in tissues.",
keywords = "epigenomics, gene regulation, single cell, skin, stem cell",
author = "Sai Ma and Bing Zhang and LaFave, {Lindsay M.} and Earl, {Andrew S.} and Zachary Chiang and Yan Hu and Jiarui Ding and Alison Brack and Kartha, {Vinay K.} and Tristan Tay and Travis Law and Caleb Lareau and Hsu, {Ya Chieh} and Aviv Regev and Buenrostro, {Jason D.}",
note = "Funding Information: We thank members of the Regev and Buenrostro labs for critical reading of the manuscript and helpful discussions. We are grateful to Jonathan Strecker for providing Tn5 and the Bauer Core at Harvard for providing sequencing services. J.D.B. and the Buenrostro lab acknowledge support from the Allen Distinguished Investigator Program through the Paul G. Allen Frontiers Group , the Chan Zuckerberg Initiative , and the NIH New Innovator Award (DP2). A.R. is an Investigator of the Howard Hughes Medical Institute. Work was supported by the NHGRI Center for Cell Circuits (to A.R.), the Klarman Cell Observatory (to A.R.), a grant from the BRAIN Initiative (to A.R.), the Smith Family Foundation Odyssey Award (to Y.-C.H.), and NIH R01-AR070825 (to Y.-C.H.). Y.-C.H. is a Pew Scholar and a NYSCF – Robertson Investigator. B.Z. is an awardee of the Charles A. King Trust postdoctoral research fellowship. Funding Information: We thank members of the Regev and Buenrostro labs for critical reading of the manuscript and helpful discussions. We are grateful to Jonathan Strecker for providing Tn5 and the Bauer Core at Harvard for providing sequencing services. J.D.B. and the Buenrostro lab acknowledge support from the Allen Distinguished Investigator Program through the Paul G. Allen Frontiers Group, the Chan Zuckerberg Initiative, and the NIH New Innovator Award (DP2). A.R. is an Investigator of the Howard Hughes Medical Institute. Work was supported by the NHGRI Center for Cell Circuits (to A.R.), the Klarman Cell Observatory (to A.R.), a grant from the BRAIN Initiative (to A.R.), the Smith Family Foundation Odyssey Award (to Y.-C.H.), and NIH R01-AR070825 (to Y.-C.H.). Y.-C.H. is a Pew Scholar and a NYSCF ? Robertson Investigator. B.Z. is an awardee of the Charles A. King Trust postdoctoral research fellowship. S.M. developed the protocol and generated datasets. B.Z. and L.M.L. collected mouse tissues. Z.C. Y.H. V.K.K. C.L. A.S.E. T.T. Y.-C.H. and J.D. provided computational support. A.B. and T.L. helped with experimental design. S.M. and J.D.B. conducted the data analysis with input from A.R. J.D.B. A.R. and S.M. wrote the manuscript. J.D.B. and A.R. supervised the research, and all authors reviewed the manuscript. A.R. is a founder and equity holder of Celsius Therapeutics, is an equity holder in Immunitas Therapeutics, and until August 31, 2020, was an SAB member of Syros Pharmaceuticals, Neogene Therapeutics, Asimov, and ThermoFisher Scientific. From August 1, 2020, A.R. is an employee of Genentech. J.D.B. holds patents related to ATAC-seq and is an SAB member of Camp4 and seqWell. J.D.B. A.R. and S.M. submitted a provisional patent application based on this work. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = nov,
day = "12",
doi = "10.1016/j.cell.2020.09.056",
language = "English (US)",
volume = "183",
pages = "1103--1116.e20",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}