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Status |
Public on Apr 16, 2019 |
Title |
Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here we present a massively parallel droplet-based platform for mapping transposase-accessible chromatin in tens of thousands of single cells per sample (scATAC-seq). We obtain and analyze chromatin profiles of over 200,000 single cells in two primary human systems. In blood, scATAC-seq allows marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity, and reconstruction of trajectories of differentiation from progenitors to diverse and rare immune cell types. In basal cell carcinoma, scATAC-seq reveals regulatory landscapes of malignant, stromal, and immune cell types in the tumor microenvironment. Moreover, scATAC-seq of serial tumor biopsies before and after PD-1 blockade allows identification of chromatin regulators and differentiation trajectories of therapy-responsive intratumoral T cell subsets, revealing a shared regulatory program driving CD8+ T cell exhaustion and CD4+ T follicular helper cell development in association with clinical response. We anticipate that droplet-based single-cell chromatin accessibility will provide a broadly applicable means of identifying regulatory factors and elements that underlie cell type and function.
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Overall design |
We used scATAC product from 10x Genomics to profile cell lines, human immune cells and solid biopsies from basal cell carcinoma patients before and after immunotherapy treatment.
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Contributor(s) |
Granja J, Zheng G, Shah P |
Citation(s) |
31375813 |
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Submission date |
Apr 14, 2019 |
Last update date |
Nov 04, 2022 |
Contact name |
Preyas Shah |
Organization name |
10x Genomics
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Street address |
7068 Koll Center Pkwy #401
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City |
Pleasanton |
ZIP/Postal code |
94566 |
Country |
USA |
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Platforms (2) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL16512 |
Illumina HiSeq 2000 (Homo sapiens; Mus musculus) |
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Samples (67)
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Relations |
BioProject |
PRJNA532774 |
SRA |
SRP192525 |
Supplementary file |
Size |
Download |
File type/resource |
GSE129785_RAW.tar |
66.7 Gb |
(http)(custom) |
TAR (of TSV) |
GSE129785_scATAC-Hematopoiesis-All.cell_barcodes.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-Hematopoiesis-All.mtx.gz |
6.0 Gb |
(ftp)(http) |
MTX |
GSE129785_scATAC-Hematopoiesis-All.peaks.txt.gz |
4.3 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-Hematopoiesis-CD34.cell_barcodes.txt.gz |
848.7 Kb |
(ftp)(http) |
TXT |
GSE129785_scATAC-Hematopoiesis-CD34.mtx.gz |
506.4 Mb |
(ftp)(http) |
MTX |
GSE129785_scATAC-Hematopoiesis-CD34.peaks.txt.gz |
4.3 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-PBMCs-Fresh.cell_barcodes.txt.gz |
192.2 Kb |
(ftp)(http) |
TXT |
GSE129785_scATAC-PBMCs-Fresh.mtx.gz |
414.9 Mb |
(ftp)(http) |
MTX |
GSE129785_scATAC-PBMCs-Fresh.peaks.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-PBMCs-Frozen.cell_barcodes.txt.gz |
228.2 Kb |
(ftp)(http) |
TXT |
GSE129785_scATAC-PBMCs-Frozen.mtx.gz |
209.2 Mb |
(ftp)(http) |
MTX |
GSE129785_scATAC-PBMCs-Frozen.peaks.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-PBMCs-FrozenSort.cell_barcodes.txt.gz |
207.4 Kb |
(ftp)(http) |
TXT |
GSE129785_scATAC-PBMCs-FrozenSort.mtx.gz |
319.4 Mb |
(ftp)(http) |
MTX |
GSE129785_scATAC-PBMCs-FrozenSort.peaks.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-TME-All.cell_barcodes.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-TME-All.mtx.gz |
4.5 Gb |
(ftp)(http) |
MTX |
GSE129785_scATAC-TME-All.peaks.txt.gz |
4.4 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-TME-TCells.cell_barcodes.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
GSE129785_scATAC-TME-TCells.mtx.gz |
2.9 Gb |
(ftp)(http) |
MTX |
GSE129785_scATAC-TME-TCells.peaks.txt.gz |
4.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |