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Title: Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer
Author: 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
Keywords: Càncer colorectal
Cèl·lules mare
Transcripció genètica
Colorectal cancer
Stem cells
Genetic transcription
Issue Date: 11-May-2020
Publisher: Elsevier
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Cell Stem Cell, 26, June, 2020
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ISSN: 1934-5909
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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