Health & Environmental Research Online (HERO)


Print Feedback Export to File
7424315 
Journal Article 
High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer 
Grosselin, K; Durand, A; Marsolier, J; Poitou, A; Marangoni, E; Nemati, F; Dahmani, A; Lameiras, S; Reyal, F; Frenoy, O; Pousse, Y; Reichen, M; Woolfe, A; Brenan, C; Griffiths, AD; Vallot, C; Gérard, A; , 
2019 
1 
Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718 
NATURE PUBLISHING GROUP 
NEW YORK 
51 
6 
1060-1066 
English 
31152164 
WOS:000469996900018 
Modulation of chromatin structure via histone modification is a major epigenetic mechanism and regulator of gene expression. However, the contribution of chromatin features to tumor heterogeneity and evolution remains unknown. Here we describe a high-throughput droplet microfluidics platform to profile chromatin landscapes of thousands of cells at single-cell resolution. Using patient-derived xenograft models of acquired resistance to chemotherapy and targeted therapy in breast cancer, we found that a subset of cells within untreated drug-sensitive tumors share a common chromatin signature with resistant cells, undetectable using bulk approaches. These cells, and cells from the resistant tumors, have lost chromatin marks-H3K27me3, which is associated with stable transcriptional repression-for genes known to promote resistance to treatment. This single-cell chromatin immunoprecipitation followed by sequencing approach paves the way to study the role of chromatin heterogeneity, not just in cancer but in other diseases and healthy systems, notably during cellular differentiation and development.