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.

结直肠癌 (CRC) 由具有不同基因型和表型的细胞的混合物组成。在这里，我们揭示了 CRC 细胞生物合成能力中以前未被认识的异质性。我们发现 CRC 中的大部分核糖体 DNA 转录和蛋白质合成发生在有限的肿瘤细胞亚群中，这些肿瘤细胞定位于特定的生态位。作为分化的结果，其余的肿瘤细胞经历了不可逆的生物合成能力丧失。生物合成结构域内的癌细胞的特点是 RNA 聚合酶 I 亚基 A (POLR1A) 水平升高。POLR1A 高细胞群的基因消融对 CRC 施加了不可逆的生长停滞。我们表明，升高的生物合成定义了 LGR5 ⁺和 LGR5 ^-的干性肿瘤细胞。因此，CRC 中的常见架构是基于转录核糖体 DNA 和合成蛋白质的差异能力的简单细胞层次结构。