Advanced Science (Jun 2024)
Integrative Single Cell Atlas Revealed Intratumoral Heterogeneity Generation from an Adaptive Epigenetic Cell State in Human Bladder Urothelial Carcinoma
- Yu Xiao,
- Wan Jin,
- Kaiyu Qian,
- Lingao Ju,
- Gang Wang,
- Kai Wu,
- Rui Cao,
- Luyuan Chang,
- Zilin Xu,
- Jun Luo,
- Liuying Shan,
- Fang Yu,
- Xintong Chen,
- Dongmei Liu,
- Hong Cao,
- Yejinpeng Wang,
- Xinyue Cao,
- Wei Zhou,
- Diansheng Cui,
- Ye Tian,
- Chundong Ji,
- Yongwen Luo,
- Xin Hong,
- Fangjin Chen,
- Minsheng Peng,
- Yi Zhang,
- Xinghuan Wang
Affiliations
- Yu Xiao
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Wan Jin
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Kaiyu Qian
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Lingao Ju
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Gang Wang
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Kai Wu
- Euler Technology Beijing 102206 China
- Rui Cao
- Department of Urology Beijing Friendship Hospital Capital Medical University Beijing 100050 China
- Luyuan Chang
- Euler Technology Beijing 102206 China
- Zilin Xu
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Jun Luo
- Department of Pathology Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Liuying Shan
- Euler Technology Beijing 102206 China
- Fang Yu
- Department of Pathology Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Xintong Chen
- Euler Technology Beijing 102206 China
- Dongmei Liu
- Euler Technology Beijing 102206 China
- Hong Cao
- Department of Pathology Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Yejinpeng Wang
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Xinyue Cao
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Wei Zhou
- Hubei Key Laboratory of Medical Technology on Transplantation Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University Wuhan 430071 China
- Diansheng Cui
- Department of Urology Hubei Cancer Hospital Wuhan 430079 China
- Ye Tian
- Department of Urology Beijing Friendship Hospital Capital Medical University Beijing 100050 China
- Chundong Ji
- Department of Urology The Affiliated Hospital of Panzhihua University Panzhihua 617099 China
- Yongwen Luo
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- Xin Hong
- Department of Urology Peking University International Hospital Beijing 102206 China
- Fangjin Chen
- Center for Quantitative Biology School of Life Sciences Peking University Beijing 100091 China
- Minsheng Peng
- State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650201 China
- Yi Zhang
- Euler Technology Beijing 102206 China
- Xinghuan Wang
- Department of Urology, Hubei Key Laboratory of Urological Diseases, Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province Zhongnan Hospital of Wuhan University Wuhan 430071 China
- DOI
- https://doi.org/10.1002/advs.202308438
- Journal volume & issue
-
Vol. 11,
no. 24
pp. n/a – n/a
Abstract
Abstract Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1‐positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low‐grade noninvasive and high‐grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial‐to‐mesenchymal transition generated TPCS. TPCS has stem‐cell‐like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell‐like epigenomic landscape, which might generate ITH without additional genetic diversification.
Keywords
- adaptive immunity
- bladder cancer
- intratumor heterogeneity
- single cell
- TM4SF1‐positive cancer subpopulation
