Abstract

A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not yet been fully characterized in human cells. Here, we collected ATAC-seq and RNA-seq data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including a large class of response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Use of allele-specific read-mapping identified thousands of variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a broad resource of chromatin landscape dynamics and highlight the need for large-scale characterization of effects of genetic variation in stimulated cells.

Genome browser tracks

ATAC-seq visualization of chromatin accessibility as genome browser tracks. Use the following link to add tracks to a UCSC browser. Alternatively click the following link to open the UCSC browser with the tracks already added.

Shiny app

Please try our shiny app (accessible through the following link) where one can interactively visualize gene expression and allele-specific chromatin accessibility.

Raw data download

The ATAC-seq and RNA-seq data generated by this study is available on GEO under accession GSE118189 and GSE118165, respectively. We also used ATAC-seq from previous studies, available under GEO accession GSE74912. Additionally, raw ChIP-seq data for p50 and p65 subunits of NFkB1 in stimulated CD4+ T cells is available under GSE126505.

Thymocyte and TEC data

MACS2-identified peaks (fetal_MACS2_peaks) and ATAC-seq read counts (fetal_ATAC_counts.txt) for fetal tissue samples.

Supplemental files

In total we have 6 supplemental files:

  1. Supplementary_tables.xlsx - Master file of supplementary information.
  2. Supplementary_data_1_ATAC_differentiation_DA_peaks.txt - Significant differentially accessible regions when comparing cell subset to progenitor.
  3. Supplementary_data_2_RNA_differentiation_DE_genes.txt - Significant differentially expressed genes when comparing cell subset to progenitor.
  4. Supplementary_data_3_ATAC_stimulation_DA_peaks.txt - Significant differentially accessible regions under stimulation.
  5. Supplementary_data_4_RNA_stimulation_DE_genes.txt - Significant differentially expressed genes under stimulation.
  6. Supplementary_data_5_aggregated_gwas_asc_da_de.txt - Table with genome-wide significant GWAS, variants with allele-specific chromatin accessibility that disrupt PWM-predicted TF binding, regions of differential accessibility, and nearby differentially expressed genes.

Citation

If you use this resource in your research, please cite:

Calderon, Diego, Michelle LT Nguyen, Anja Mezger, Arwa Kathiria, Vinh Nguyen, Ninnia Lescano, Beijing Wu et al. "Landscape of stimulation-responsive chromatin across diverse human immune cells." bioRxiv (2018): 409722.

Contact

For questions please contact Diego Calderon (dcal@stanford.edu).