该研究组对独立的无主题皮肤干细胞群体进行荧光谱系追踪、单细胞转录组学和双工测序，以确定化学诱导皮肤肿瘤的起源。肿瘤主要来自上毛囊的Lgr6+和/或Lrig1+干细胞，但很少来自Lgr5+和Krt19+毛囊凸起。二甲苯并蒽启动的Lgr6+干细胞对肿瘤启动子治疗有应答，导致携带典型Hras Q61L突变的启动细胞克隆扩增。Kras中的自发突变也会克隆扩增，但除非删除Hras基因，否则不会产生肿瘤，这表明Hras和Kras途径之间存在竞争性相互作用，影响克隆选择。
据介绍，肿瘤细胞起源的鉴定是癌症生物学中的一个基本问题。
附：英文原文
Title: Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle
Author: Eve Kandyba, Arnaud Jabouille, Ferriol Calvet, Yun Rose Li, Andrea Curtabbi, Diana Cristea, Joyce Shin, Reyno Delrosario, Jonathan Anzules, Di Wu, David Quigley, Mark Taylor, Camila Zanette, Fang Yin Lo, Jacob Higgins, Jesse Salk, Nuria Lopez-Bigas, Allan Balmain
Issue&Volume: 2026-06-11
Abstract: The identification of the cancer cell of origin is a fundamental question in cancer biology. We used fluorescent lineage tracing of independent mouse skin stem cell populations, single cell transcriptomics, and Duplex sequencing, to identify the origin of chemically induced skin tumors. Tumors arose predominantly from Lgr6+ and / or Lrig1+ stem cells of the upper hair follicle, but only very rarely from the Lgr5+ and Krt19+ hair follicle bulge. Lgr6+ stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical Hras Q61L mutation. Spontaneous mutations in Kras also clonally expanded, but did not generate tumors unless the Hras gene was deleted, thus revealing a competitive interaction between Hras and Kras pathways that influences clonal selection.
DOI: adv8291
Source: https://www.science.org/doi/10.1126/science.adv8291