Journal
CELL STEM CELL
Volume 26, Issue 6, Pages 845-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2020.04.012
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Funding
- Ministerio de Economia y Competitividad (MINECO, Spain) [SAF2017-89109-P]
- Instituto de Salud Carlos III (ISCIII, Spain) [CP14/00229]
- Agencia Estatal de Investigacion (AEI, Spain) [CP14/00229]
- Fondo Europeo de Desarrollo Regional (FEDER, European Union) [CP14/00229]
- European Research Council [ERC AdvG 340176]
- WorldWide Cancer Research (WWCR, European Union) [12_1209]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR, Spain) [2017 SGR 698]
- Fondo de Investigaciones Sanitarias (FIS, Spain) [PI16-01898]
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Colorectal 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 (PURI A). 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.
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