Morral, ClaraStanisavljevic, JelenaHernando Momblona, XavierMereu, ElisabettaÁlvarez Varela, AdriánCortina, CarmeStork, DianaSlebe, FelipeTuron, GemmaWhissell, GavinSevillano, MartaMerlos Suárez, AnnaCasanova Martí, AngelaMoutinho, CátiaLowe, Scott W.Dow, Lukas E.Villanueva Garatachea, AlbertoSancho, ElenaHeyn, HolgerBatlle, Eduard2020-05-152021-05-112020-05-111934-5909https://hdl.handle.net/2445/160426Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA polymerase I subunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest on CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5− tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins.17 p.application/pdfengcc-by-nc-nd (c) Elsevier, 2020http://creativecommons.org/licenses/by-nc-nd/3.0/es/Càncer colorectalCèl·lules mareTranscripció genèticaColorectal cancerStem cellsGenetic transcriptioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess