| Literature DB >> 34939038 |
Catherine Gutierrez1,2,3, Aziz M Al'Khafaji4,5,6,3, Eric Brenner4,5,3, Kaitlyn E Johnson5, Satyen H Gohil1,2,6,7,8, Ziao Lin1,6,9, Binyamin A Knisbacher6, Russell E Durrett4,5, Shuqiang Li2,6,10, Salma Parvin2, Anat Biran2,6, Wandi Zhang2, Laura Rassenti11, Thomas J Kipps11, Kenneth J Livak2,10, Donna Neuberg12, Anthony Letai1,2, Gad Getz1,6,13,14, Catherine J Wu1,2,6,15, Amy Brock4,5.
Abstract
Lineage-tracing methods have enabled characterization of clonal dynamics in complex populations, but generally lack the ability to integrate genomic, epigenomic and transcriptomic measurements with live-cell manipulation of specific clones of interest. We developed a functionalized lineage-tracing system, ClonMapper, which integrates DNA barcoding with single-cell RNA sequencing and clonal isolation to comprehensively characterize thousands of clones within heterogeneous populations. Using ClonMapper, we identified subpopulations of a chronic lymphocytic leukemia cell line with distinct clonal compositions, transcriptional signatures and chemotherapy survivorship trajectories; patterns that were also observed in primary human chronic lymphocytic leukemia. The ability to retrieve specific clones before, during and after treatment enabled direct measurements of clonal diversification and durable subpopulation transcriptional signatures. ClonMapper is a powerful multifunctional approach to dissect the complex clonal dynamics of tumor progression and therapeutic response.Entities:
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Year: 2021 PMID： 34939038 PMCID： PMC8691751 DOI： 10.1038/s43018-021-00222-8
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347