Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer

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 occur...

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Bibliographic Details
Authors: 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
Format: article
Status:Versión aceptada para publicación
Publication Date:2020
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/160426
Online Access:https://hdl.handle.net/2445/160426
Access Level:Open access
Keyword:Càncer colorectal
Cèl·lules mare
Transcripció genètica
Colorectal cancer
Stem cells
Genetic transcription
Description
Summary: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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