Journal article
Non-genetic determinants of malignant clonal fitness at single-cell resolution
KA Fennell, D Vassiliadis, EYN Lam, LG Martelotto, JJ Balic, S Hollizeck, TS Weber, T Semple, Q Wang, DC Miles, L MacPherson, YC Chan, AA Guirguis, LM Kats, ES Wong, SJ Dawson, SH Naik, MA Dawson
Nature | NATURE PORTFOLIO | Published : 2022
Abstract
All cancers emerge after a period of clonal selection and subsequent clonal expansion. Although the evolutionary principles imparted by genetic intratumour heterogeneity are becoming increasingly clear1, little is known about the non-genetic mechanisms that contribute to intratumour heterogeneity and malignant clonal fitness2. Here, using single-cell profiling and lineage tracing (SPLINTR)—an expressed barcoding strategy—we trace isogenic clones in three clinically relevant mouse models of acute myeloid leukaemia. We find that malignant clonal dominance is a cell-intrinsic and heritable property that is facilitated by the repression of antigen presentation and increased expression of the sec..
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Awarded by Victorian Cancer Agency
Funding Acknowledgements
We thank members of the Dawson laboratory, particularly S. Jackson, O. Gilan and K. Knezevic for technical assistance with experiments; F. Rossello for advice and discussions related to data analysis and D. Zalcenstein and J. Gao for advice regarding lentiviral barcode design and cloning. We thank the following funders for fellowship and grant support: Peter MacCallum Foundation Grant (to D.V.), VCA mid-career fellowship (to E.Y.N.L.), CSIRO Future Science Fellowship in Synthetic Biology (to T.S.W.), NHMRC Early Career Fellowship grant (no. 1052195, to D.C.M.) NHMRC Investigator Grant (no. 1196749, to M.A.D.), Cancer Council Victoria Dunlop Fellowship (to M.A.D), Howard Hughes Medical Institute international research scholarship (no. 55008729, to M.A.D), NHMRC Investigator Grant (no. 1196755, to S.J.D.), CSL Centenary fellowship (to S.J.D.) and NHMRC Project Grant (no. 1128984, to S.J.D. and M.A.D.).