Open AccessSingle-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression
Author(s) -
Steven J. Wu,
Scott N. Furlan,
Anca B. Mihalas,
Hatice S Kaya-Okur,
Abdullah H. Feroze,
Samuel Emerson,
Yi Zheng,
K. Jane Carson,
Patrick J. Cimino,
C. Dirk Keene,
Jay F. Sarthy,
Raphaël Gottardo,
Kami Ahmad,
Steven Henikoff,
Anoop P. Patel
Publication year - 2021
Publication title -
nature biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.358
H-Index - 445
eISSN - 1546-1696
pISSN - 1087-0156
DOI - 10.1038/s41587-021-00865-z
Subject(s) - chromatin , histone , biology , embryonic stem cell , single cell analysis , cell type , cell , microbiology and biotechnology , cellular differentiation , computational biology , genetics , gene
Methods for quantifying gene expression 1 and chromatin accessibility 2 in single cells are well established, but single-cell analysis of chromatin regions with specific histone modifications has been technically challenging. In this study, we adapted the CUT&Tag method 3 to scalable nanowell and droplet-based single-cell platforms to profile chromatin landscapes in single cells (scCUT&Tag) from complex tissues and during the differentiation of human embryonic stem cells. We focused on profiling polycomb group (PcG) silenced regions marked by histone H3 Lys27 trimethylation (H3K27me3) in single cells as an orthogonal approach to chromatin accessibility for identifying cell states. We show that scCUT&Tag profiling of H3K27me3 distinguishes cell types in human blood and allows the generation of cell-type-specific PcG landscapes from heterogeneous tissues. Furthermore, we used scCUT&Tag to profile H3K27me3 in a patient with a brain tumor before and after treatment, identifying cell types in the tumor microenvironment and heterogeneity in PcG activity in the primary sample and after treatment.