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Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer 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 Càncer colorectal Cèl·lules mare Transcripció genètica Colorectal cancer Stem cells Genetic transcription 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. 2020-05-15T11:54:19Z 2021-05-11T05:10:17Z 2020-05-11 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 1934-5909 https://hdl.handle.net/2445/160426 eng Versió postprint del document publicat a: https://doi.org/10.1016/j.stem.2020.04.012 Cell Stem Cell, 26, June, 2020 https://doi.org/10.1016/j.stem.2020.04.012 cc-by-nc-nd (c) Elsevier, 2020 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess 17 p. application/pdf Elsevier Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))