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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/160426
Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer
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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 (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.
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MORRAL, Clara, STANISAVLJEVIC, Jelena, HERNANDO MOMBLONA, Xavier, MEREU, Elisabetta, ÁLVAREZ VARELA, Adrián, CORTINA, Carme, STORK, Diana, SLEBE, Felipe, TURON, Gemma, WHISSELL, Gavin, SEVILLANO, Marta, MERLOS SUÁREZ, Anna, CASANOVA MARTÍ, Angela, MOUTINHO, Cátia, LOWE, Scott w., DOW, Lukas e., VILLANUEVA GARATACHEA, Alberto, SANCHO, Elena, HEYN, Holger, BATLLE, Eduard. Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer. _Cell Stem Cell_. 26. Vol. June, núm. 2020. [consulta: 24 de gener de 2026]. ISSN: 1934-5909. [Disponible a: https://hdl.handle.net/2445/160426]