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Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression
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Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression
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Journal Article
Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression
2021
Overview
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.
An improved method for single-cell analysis of histone modifications is applied to stem cell differentiation and cancer.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Analysis
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Brain Neoplasms - metabolism
/ Genes
/ Histones
/ Humans
/ Identification and classification
/ Jumonji Domain-Containing Histone Demethylases - genetics
/ Jumonji Domain-Containing Histone Demethylases - metabolism
/ Letter
/ Methods
/ Polycomb-Group Proteins - genetics
/ Polycomb-Group Proteins - metabolism
/ Tumors
