Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation

被引：213

作者：

Preissl, Sebastian ^{[1
,2
]}

Fang, Rongxin ^{[1
,3
]}

Huang, Hui ^{[1
,4
]}

Zhao, Yuan ^{[1
,3
]}

Raviram, Ramya ^{[1
]}

Gorkin, David U. ^{[1
,2
]}

Zhang, Yanxiao ^{[1
]}

Sos, Brandon C. ^{[4
,5
]}

Afzal, Veena ^{[6
]}

Dickel, Diane E. ^{[6
]}

Kuan, Samantha ^{[1
]}

Visel, Axel ^{[6
,7
,8
]}

Pennacchio, Len A. ^{[6
,7
,9
]}

Zhang, Kun ^{[5
]}

Ren, Bing ^{[1
,2
,10
]}

机构：

[1] Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Ctr Epigen, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA

[6] Lawrence Berkeley Natl Lab, Environm Genom & Syst Biol Div, Berkeley, CA USA

[7] US DOE, Joint Genome Inst, Walnut Creek, CA USA

[8] Univ Calif Merced, Sch Nat Sci, Merced, CA USA

[9] Univ Calif Berkeley, Comparat Biochem Program, Berkeley, CA 94720 USA

[10] Univ Calif San Diego, Sch Med, Inst Genom Med, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

NATURE NEUROSCIENCE | 2018年 / 21卷 / 03期

关键词：

NEURONAL SUBTYPES; DNA; BINDING; EXPRESSION; LANDSCAPE; DIVERSITY; ELEMENTS; DATABASE; DIFFERENTIATION; IDENTIFICATION;

D O I：

10.1038/s41593-018-0079-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

引用

页码：432 / +

页数：14

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