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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Nature Genetics; v. 52, n. 11, p. 1208+, NOV 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 17/24287-8 - O papel de elementos do microambiente tumoral na plasticidade e heterogeneidade de células malignas
• Beneficiário: Gabriela Sarti Kinker
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 14/27287-0 - Caracterização do sistema melatonérgico de gliomas humanos e sua implicação sobre o grau de agressividade e invasibilidade tumoral
• Beneficiário: Gabriela Sarti Kinker
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto