Single-cell epigenomic variability reveals functional cancer heterogeneity

DSpace/Manakin Repository

Single-cell epigenomic variability reveals functional cancer heterogeneity

Citable link to this page

 

 
Title: Single-cell epigenomic variability reveals functional cancer heterogeneity
Author: Litzenburger, Ulrike M.; Buenrostro, Jason D.; Wu, Beijing; Shen, Ying; Sheffield, Nathan C.; Kathiria, Arwa; Greenleaf, William J.; Chang, Howard Y.

Note: Order does not necessarily reflect citation order of authors.

Citation: Litzenburger, Ulrike M., Jason D. Buenrostro, Beijing Wu, Ying Shen, Nathan C. Sheffield, Arwa Kathiria, William J. Greenleaf, and Howard Y. Chang. 2017. “Single-cell epigenomic variability reveals functional cancer heterogeneity.” Genome Biology 18 (1): 15. doi:10.1186/s13059-016-1133-7. http://dx.doi.org/10.1186/s13059-016-1133-7.
Full Text & Related Files:
Abstract: Background: Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally. Results: We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high versus low cells prospectively isolated GATA1 and GATA2 high versus low cells. GATA high versus low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity. Conclusion: Single-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1133-7) contains supplementary material, which is available to authorized users.
Published Version: doi:10.1186/s13059-016-1133-7
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259890/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371142
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters