结直肠癌
转移
癌症研究
生物
癌症
医学
肿瘤科
遗传学
作者
Shanshan Chao,Fei Zhang,Huiwen Yan,Liuyang Wang,Liwen Zhang,Zhi Wang,Rui Xue,Lei Wang,Zhenzhen Wu,Bing Jiang,Guizhi Shi,Yuanchao Xue,Jun Du,Pengcheng Bu
出处
期刊:EMBO Reports
[Springer Nature]
日期:2023-06-20
卷期号:24 (8)
被引量:6
标识
DOI:10.15252/embr.202256416
摘要
Intratumor heterogeneity (ITH) is a barrier to effective therapy. However, it is largely unknown how ITH is established at the onset of tumor progression, such as in colorectal cancer (CRC). Here, we integrate single-cell RNA-seq and functional validation to show that asymmetric division of CRC stem-like cells (CCSC) is critical for early ITH establishment. We find that CCSC-derived xenografts contain seven cell subtypes, including CCSCs, that dynamically change during CRC xenograft progression. Furthermore, three of the subtypes are generated by asymmetric division of CCSCs. They are functionally distinct and appear at the early stage of xenografts. In particular, we identify a chemoresistant and an invasive subtype, and investigate the regulators that control their generation. Finally, we show that targeting the regulators influences cell subtype composition and CRC progression. Our findings demonstrate that asymmetric division of CCSCs contributes to the early establishment of ITH. Targeting asymmetric division may alter ITH and benefit CRC therapy.
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