Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pan-cancer single-cell RNA-seq identifies recurring programs of cellular heterogeneity

Full text
Author(s):
Show less -
Kinker, Gabriela S. [1, 2] ; Greenwald, Alissa C. [2] ; Tal, Rotem [2] ; Orlova, Zhanna [2] ; Cuoco, Michael S. [3] ; McFarland, James M. [4] ; Warren, Allison [4] ; Rodman, Christopher [3] ; Roth, Jennifer A. [4] ; Bender, Samantha A. [4] ; Kumar, Bhavna [5] ; Rocco, James W. [5] ; Fernandes, Pedro A. C. M. [1] ; Mader, Christopher C. [4] ; Keren-Shaul, Hadas [6, 7] ; Plotnikov, Alexander [7] ; Barr, Haim [7] ; Tsherniak, Aviad [4] ; Rozenblatt-Rosen, Orit [3] ; Krizhanovsky, Valery [2] ; Puram, V, Sidharth ; Regev, Aviv [8, 3] ; Tirosh, Itay [2]
Total Authors: 23
Affiliation:
[1] Univ Sao Paulo, Inst Biosci, Sao Paulo - Brazil
[2] Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot - Israel
[3] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 - USA
[4] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 - USA
[5] Ohio State Univ, Dept Otolaryngol Head & Neck Surg, Wexner Med Ctr, Columbus, OH - USA
[6] Weizmann Inst Sci, Life Sci Core Facil, Rehovot - Israel
[7] Weizmann Inst Sci, Nancy & Stephen Grand Israel Natl Ctr Personalize, Rehovot - Israel
[8] Genentech Inc, San Francisco, CA - USA
Total Affiliations: 8
Document type: Journal article
Source: Nature Genetics; v. 52, n. 11, p. 1208+, NOV 2020.
Web of Science Citations: 0
Abstract

Single-cell RNA-seq of a collection of 200 cancer cell lines finds common, recurrent heterogeneous expression programs, which also are found in patient samples and are linked to cell state and drug sensitivity. Cultured cell lines are the workhorse of cancer research, but the extent to which they recapitulate the heterogeneity observed among malignant cells in tumors is unclear. Here we used multiplexed single-cell RNA-seq to profile 198 cancer cell lines from 22 cancer types. We identified 12 expression programs that are recurrently heterogeneous within multiple cancer cell lines. These programs are associated with diverse biological processes, including cell cycle, senescence, stress and interferon responses, epithelial-mesenchymal transition and protein metabolism. Most of these programs recapitulate those recently identified as heterogeneous within human tumors. We prioritized specific cell lines as models of cellular heterogeneity and used them to study subpopulations of senescence-related cells, demonstrating their dynamics, regulation and unique drug sensitivities, which were predictive of clinical response. Our work describes the landscape of heterogeneity within diverse cancer cell lines and identifies recurrent patterns of heterogeneity that are shared between tumors and specific cell lines. (AU)

FAPESP's process: 17/24287-8 - The role of tumor microenvironment elements in malignant cell plasticity and heterogeneity
Grantee:Gabriela Sarti Kinker
Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
FAPESP's process: 14/27287-0 - Characterization of the melatonergic system of human gliomas and its implication on tumor aggressiveness and invasiveness
Grantee:Gabriela Sarti Kinker
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)