|
| Status |
Public on Jun 08, 2018 |
| Title |
Histone Variant H2A.Z Defines Cell Identity in Vascular Smooth Muscle Cells as Revealed by Single-Cell Transcriptomics |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
We applied single-cell RNA-Seq to analyze human diseased arteries, and identified histone variant H2A.Z as a key histone signature to maintain vascular smooth muscle cell (VSMC) identity. We show that H2A.Z occupies genomic regions near VSMC marker genes and its occupancy is decreased in VSMC undergoing dedifferentiation. Mechanistically, H2A.Z occupancy preferentially promotes nucleosome turnover, facilitates the recruitment of Smad3 and Med1 to VSMC marker genes, thereby activating gene expression. In human diseased vascular tissue, H2A.Z expression dramatically decreased. Notably, in vivo overexpression of H2A.Z rescued injury-induced loss of VSMC identity and neointima formation. Together, our data introduce dynamic occupancy of histone variant as a novel regulatory basis contributing to cell fate decisions, and imply H2A.Z as a potential intervention node for vascular diseases.
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| Overall design |
Single-cell RNA-seq of human diseased arteries; ChIP-seq of H2A.Z, SMAD3, SRF and MED1 in wild-type cultured vscular smooth muscle cells;VSMC nucleosome occupancy by Mnase.
Please note that, given the number of raw files associated with each sample, two sample records have been created for each scRNA-seq sample (e.g. SC_92467_1 & _2, SC_92558_1 & _2).
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| Contributor(s) |
Wang L, Yu P, Yao F, Yuan X |
| Citation(s) |
29871976 |
| |
| Submission date |
Mar 28, 2018 |
| Last update date |
Mar 26, 2019 |
| Contact name |
Li Wang |
| Organization name |
NIH
|
| Street address |
111 T.W. Alexander Dr
|
| City |
Durham |
| ZIP/Postal code |
27709 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (52)
|
|
| Relations |
| BioProject |
PRJNA445961 |
| SRA |
SRP136608 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE112417_H2AZKD_mm9_rnaseq.bigWig |
162.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_NT_mm9_rnaseq.bigWig |
161.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_RAW.tar |
9.7 Gb |
(http)(custom) |
TAR (of BIGWIG) |
| GSE112417_VSMC_FBS_starve_rna_logFC.txt.gz |
238.8 Kb |
(ftp)(http) |
TXT |
| GSE112417_VSMC_H2AZ_ChIP.bigWig |
635.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_VSMC_H2AZ_Input.bigWig |
544.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_VSMC_P10_RNAseq.bigWig |
209.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_VSMC_P1_RNAseq.bigWig |
232.2 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_VSMC_sc_umi.csv.gz |
2.2 Mb |
(ftp)(http) |
CSV |
| GSE112417_shH2AZ_Input.bigWig |
652.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shH2AZ_Med1_merge.bigWig |
413.7 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shH2AZ_SRF.bigWig |
179.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shH2AZ_Smad3_merge.bigWig |
584.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shNT_Input.bigWig |
678.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shNT_Med1_merge.bigWig |
432.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shNT_SRF.bigWig |
228.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_shNT_Smad3_merge.bigWig |
467.0 Mb |
(ftp)(http) |
BIGWIG |
| GSE112417_vsmc_singlecell_info.txt.gz |
24.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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