小柯机器人

西班牙巴塞罗那科学技术学院（BIST）Eduard Batlle研究团队取得一项新突破。他们发现核糖体DNA转录的区域划分定义了结直肠癌（CRC）中的干细胞层次结构。2020年5月11日的《细胞-干细胞》杂志发表了这项成果。

CRC由具有不同基因型和表型的细胞汞齐组成。研究人员揭示了CRC细胞的生物合成能力中以前未被认识到的异质性。他们发现，CRC中的大多数核糖体DNA转录和蛋白质合成都发生在肿瘤细胞的有限亚群中，这些亚群位于特定的位置上。其余肿瘤细胞由于分化而经历了不可逆的生物合成能力丧失。生物合成域内的癌细胞的特征是RNA聚合酶I亚基A（POLR1A）的水平升高。POLR1A高细胞群体的遗传敲除对CRC造成不可逆的生长停滞。

他们表明，提高的生物合成定义了LGR5 +和LGR5-肿瘤细胞的干性。因此，CRC中的常见体系结构是基于转录核糖体DNA和合成蛋白质的差异能力，是简单细胞层次结构。

附：英文原文

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

Author: Clara Morral, Jelena Stanisavljevic, Xavier Hernando-Momblona, Elisabetta Mereu, Adrián álvarez-Varela, Carme Cortina, Diana Stork, Felipe Slebe, Gemma Turon, Gavin Whissell, Marta Sevillano, Anna Merlos-Suárez, àngela Casanova-Martí, Catia Moutinho, Scott W. Lowe, Lukas E. Dow, Alberto Villanueva, Elena Sancho, Holger Heyn, Eduard Batlle

Issue&Volume: 2020-05-11

Abstract: Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypesand phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosyntheticcapacities of CRC cells. We discover that the majority of ribosomal DNA transcriptionand protein synthesis in CRCs occurs in a limited subset of tumor cells that localizein defined niches. The rest of the tumor cells undergo an irreversible loss of theirbiosynthetic capacities as a consequence of differentiation. Cancer cells within thebiosynthetic domains are characterized by elevated levels of the RNA polymerase Isubunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversiblegrowth arrest on CRCs. We show that elevated biosynthesis defines stemness in bothLGR5+ and LGR5 tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchybased on the differential capacity to transcribe ribosomal DNA and synthesize proteins.

DOI: 10.1016/j.stem.2020.04.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30151-X

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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