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URL: https://dx.doi.org/DOI:10.17504/protocols.io.q6gdzbw

Authors: Xingqi Chen, Ulrike Litzenburger, Yuning Wei, Alicia N. Schep, Edward L. LaGory, Hani Choudhry, Amato J. Giaccia, William J. Greenleaf, Howard Y. Chang

Group: Human Cell Atlas Method Development Community, HYChangLab

Summary: 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. PiATAC 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 HIF1A protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells.

Affiliations: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305; Dept of Genetics, Stanford University, Stanford, CA 94305; Department of Applied Physics, Stanford University, Stanford, CA 94305, Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia., Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA 94305, Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305; Dept of Genetics, Stanford University, Stanford, CA 94305; Department of Applied Physics, Stanford University, Stanford, CA 94305, Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305

External URL: https://www.biorxiv.org/content/early/2018/04/27/310359

Version: 1

Publication Date: 2018

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