生物
转录组
克拉斯
细胞分化
结直肠癌
癌症研究
癌症干细胞
癌症
癌细胞
表型
肿瘤进展
信号转导
遗传学
细胞
细胞信号
细胞生物学
基因
基因表达
作者
Thomas Sell,Christian Klotz,Matthias M. Fischer,Rosario Astaburuaga-García,Susanne M. Krug,Jarno Drost,Hans Clevers,Christine Sers,Markus Morkel,Nils Blüthgen
标识
DOI:10.1083/jcb.202204001
摘要
Colorectal cancer progression is intrinsically linked to stepwise deregulation of the intestinal differentiation trajectory. In this process, sequential mutations of APC, KRAS, TP53, and SMAD4 enable oncogenic signaling and establish the hallmarks of cancer. Here, we use mass cytometry of isogenic human colon organoids and patient-derived cancer organoids to capture oncogenic signaling, cell phenotypes, and differentiation states in a high-dimensional single-cell map. We define a differentiation axis in all tumor progression states from normal to cancer. Our data show that colorectal cancer driver mutations shape the distribution of cells along the differentiation axis. In this regard, subsequent mutations can have stem cell promoting or restricting effects. Individual nodes of the cancer cell signaling network remain coupled to the differentiation state, regardless of the presence of driver mutations. We use single-cell RNA sequencing to link the (phospho-)protein signaling network to transcriptomic states with biological and clinical relevance. Our work highlights how oncogenes gradually shape signaling and transcriptomes during tumor progression.
科研通智能强力驱动
Strongly Powered by AbleSci AI