PMID- 31611697 OWN - NLM STAT- MEDLINE DCOM- 20200128 LR - 20220417 IS - 1546-1696 (Electronic) IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 37 IP - 12 DP - 2019 Dec TI - High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell. PG - 1452-1457 LID - 10.1038/s41587-019-0290-0 [doi] AB - Single-cell RNA sequencing can reveal the transcriptional state of cells, yet provides little insight into the upstream regulatory landscape associated with open or accessible chromatin regions. Joint profiling of accessible chromatin and RNA within the same cells would permit direct matching of transcriptional regulation to its outputs. Here, we describe droplet-based single-nucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq), a method that can link a cell's transcriptome with its accessible chromatin for sequencing at scale. Specifically, accessible sites are captured by Tn5 transposase in permeabilized nuclei to permit, within many droplets in parallel, DNA barcode tagging together with the mRNA molecules from the same cells. To demonstrate the utility of SNARE-seq, we generated joint profiles of 5,081 and 10,309 cells from neonatal and adult mouse cerebral cortices, respectively. We reconstructed the transcriptome and epigenetic landscapes of major and rare cell types, uncovered lineage-specific accessible sites, especially for low-abundance cells, and connected the dynamics of promoter accessibility with transcription level during neurogenesis. FAU - Chen, Song AU - Chen S AUID- ORCID: 0000-0001-5286-3084 AD - Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. FAU - Lake, Blue B AU - Lake BB AUID- ORCID: 0000-0002-8637-9044 AD - Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. FAU - Zhang, Kun AU - Zhang K AUID- ORCID: 0000-0002-7596-5224 AD - Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. kzhang@bioeng.ucsd.edu. LA - eng GR - U01 MH114828/MH/NIMH NIH HHS/United States GR - U01 MH098977/MH/NIMH NIH HHS/United States GR - U54 HL145608/HL/NHLBI NIH HHS/United States GR - U01 DK107350/DK/NIDDK NIH HHS/United States GR - R01 HL123755/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20191014 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (Chromatin) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Chromatin/chemistry/*genetics MH - Computational Biology/*methods MH - High-Throughput Nucleotide Sequencing/*methods MH - Mice MH - RNA, Messenger/chemistry/genetics MH - Sequence Analysis, RNA/*methods MH - Transcriptome/*genetics PMC - PMC6893138 MID - NIHMS1539957 COIS- Competing financial interests: The authors declare no competing financial interests. EDAT- 2019/10/16 06:00 MHDA- 2020/01/29 06:00 PMCR- 2020/04/14 CRDT- 2019/10/16 06:00 PHST- 2019/02/21 00:00 [received] PHST- 2019/09/12 00:00 [accepted] PHST- 2019/10/16 06:00 [pubmed] PHST- 2020/01/29 06:00 [medline] PHST- 2019/10/16 06:00 [entrez] PHST- 2020/04/14 00:00 [pmc-release] AID - 10.1038/s41587-019-0290-0 [pii] AID - 10.1038/s41587-019-0290-0 [doi] PST - ppublish SO - Nat Biotechnol. 2019 Dec;37(12):1452-1457. doi: 10.1038/s41587-019-0290-0. Epub 2019 Oct 14.