Chemical genomics reveals targetable programs of human cancers rooted in pluripotency

Luca Orlando, Yannick D. Benoit, Jennifer C. Reid, Mio Nakanishi, Allison L. Boyd, Juan L. García-Rodriguez, Borko Tanasijevic, Meaghan S. Doyle, Artee Luchman, Ian J. Restall, Christopher J. Bergin, Angelique N. Masibag, Lili Aslostovar, Justin Di Lu, Sarah Laronde, Tony J. Collins, Samuel Weiss, Mickie Bhatia*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

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.

OriginalsprogEngelsk
TidsskriftCell chemical biology
Vol/bind30
Nummer7
Sider (fra-til)780-794.e8
ISSN2451-9456
DOI
StatusUdgivet - 20 jul. 2023
Udgivet eksterntJa

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