Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07115-y
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Funding
- NIH [P50-HG007735, R35-CA209919, S10OD018220]
- Parker Institute for Cancer Immunotherapy
- Swedish Research Council [VR-2016-06794, VR-2017-02074]
- King Abdulaziz University
- Swedish Research Council [2016-06794, 2017-02074] Funding Source: Swedish Research Council
- Vinnova [2017-02074] Funding Source: Vinnova
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Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1 alpha protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells.
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