Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer. Academic Article uri icon

Overview

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.

publication date

  • May 11, 2020

Research

keywords

  • Colorectal Neoplasms
  • Neoplastic Stem Cells

Identity

Scopus Document Identifier

  • 85085301169

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2020.04.012

PubMed ID

  • 32396863

Additional Document Info

volume

  • 26

issue

  • 6