Chemical genomics reveals targetable programs of human cancers rooted in pluripotency.

Autor:	Orlando L; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Benoit YD; Department of Biochemistry, McMaster University, Hamilton, ON, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada., Reid JC; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Nakanishi M; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Boyd AL; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., García-Rodriguez JL; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Tanasijevic B; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Doyle MS; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Luchman A; Arnie Charbonneau Cancer Institute & The Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada., Restall IJ; Arnie Charbonneau Cancer Institute & The Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada., Bergin CJ; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada., Masibag AN; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada., Aslostovar L; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Di Lu J; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Laronde S; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Collins TJ; Department of Biochemistry, McMaster University, Hamilton, ON, Canada., Weiss S; Arnie Charbonneau Cancer Institute & The Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada., Bhatia M; Department of Biochemistry, McMaster University, Hamilton, ON, Canada. Electronic address: mbhatia@mcmaster.ca.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2023 Jul 20; Vol. 30 (7), pp. 780-794.e8. Date of Electronic Publication: 2023 Jun 27.
DOI:	10.1016/j.chembiol.2023.06.004
Abstrakt:	Overlapping principles of embryonic and tumor biology have been described, with recent multi-omics campaigns uncovering shared molecular profiles between human pluripotent stem cells (hPSCs) and adult tumors. Here, using a chemical genomic approach, we provide biological evidence that early germ layer fate decisions of hPSCs reveal targets of human cancers. Single-cell deconstruction of hPSCs-defined subsets that share transcriptional patterns with transformed adult tissues. Chemical screening using a unique germ layer specification assay for hPSCs identified drugs that enriched for compounds that selectively suppressed the growth of patient-derived tumors corresponding exclusively to their germ layer origin. Transcriptional response of hPSCs to germ layer inducing drugs could be used to identify targets capable of regulating hPSC specification as well as inhibiting adult tumors. Our study demonstrates properties of adult tumors converge with hPSCs drug induced differentiation in a germ layer specific manner, thereby expanding our understanding of cancer stemness and pluripotency. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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