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Single-cell multi-modal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma.
Wang, Chunqing; Huang, Waidong; Zhong, Yu; Zou, Xuanxuan; Liu, Shang; Li, Jie; Sun, Yunfan; Zhou, Kaiqian; Chen, Xi; Li, Zihao; Wang, Shanshan; Huang, Yaling; Bai, Yinqi; Yin, Jianhua; Jin, Xin; Liu, Shiping; Yuan, Yue; Deng, Qiuting; Jiang, Miaomiao; Liu, Chuanyu; Liu, Longqi; Xu, Xun; Wu, Liang.
Afiliación
  • Wang C; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Huang W; BGI Research, Chongqing, China.
  • Zhong Y; BGI Research, Shenzhen, China.
  • Zou X; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Liu S; BGI Research, Chongqing, China.
  • Li J; BGI Research, Chongqing, China.
  • Sun Y; BGI Research, Chongqing, China.
  • Zhou K; BGI Research, Shenzhen, China.
  • Chen X; Department of Medical Laboratory, Hubei Provincial Clinical Research Center for Parkinson's Disease, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
  • Li Z; BGI Research, Chongqing, China.
  • Wang S; BGI Research, Shenzhen, China.
  • Huang Y; BGI Research, Shenzhen, China.
  • Bai Y; Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
  • Yin J; Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Jin X; Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
  • Liu S; Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Yuan Y; BGI Research, Chongqing, China.
  • Deng Q; BGI Research, Shenzhen, China.
  • Jiang M; BGI Research, Shenzhen, China.
  • Liu C; School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
  • Liu L; BGI Research, Shenzhen, China.
  • Xu X; BGI Research, Shenzhen, China.
  • Wu L; BGI Research, Hangzhou, China.
Clin Transl Med ; 14(9): e70000, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39210544
ABSTRACT

BACKGROUND:

Various epigenetic regulations systematically govern gene expression in cells involving various biological processes. Dysregulation of the epigenome leads to aberrant transcriptional programs and subsequently results in diseases, such as cancer. Therefore, comprehensive profiling epigenomics is essential for exploring the mechanisms underlying gene expression regulation during development and disease.

METHODS:

In this study, we developed single-cell chromatin proteins and accessibility tagmentation (scCPA-Tag), a multi-modal single-cell epigenetic profile capturing technique based on barcoded Tn5 transposases and a droplet microfluidics platform. scCPA-Tag enables the simultaneous capture of DNA profiles of histone modification and chromatin accessibility in the same cell.

RESULTS:

By applying scCPA-Tag to K562 cells and a hepatocellular carcinoma (HCC) sample, we found that the silence of several chromatin-accessible genes can be attributed to lysine-27-trimethylation of the histone H3 tail (H3K27me3) modification. We characterized the epigenetic features of the tumour cells and different immune cell types in the HCC tumour tissue by scCPA-Tag. Besides, a tumour cell subtype (C2) with more aggressive features was identified and characterized by high chromatin accessibility and a lower abundance of H3K27me3 on tumour-promoting genes.

CONCLUSIONS:

Our multi-modal scCPA-Tag provides a comprehensive approach for exploring the epigenetic landscapes of heterogeneous cell types and revealing the mechanisms of gene expression regulation during developmental and pathological processes at the single-cell level. HIGHLIGHTS scCPA-Tag offers a highly efficient and high throughput technique to simultaneously profile histone modification and chromatin accessibility within a single cell. scCPA-Tag enables to uncover multiple epigenetic modification features of cellular compositions within tumor tissues. scCPA-Tag facilitates the exploration of the epigenetic landscapes of heterogeneous cell types and provides the mechanisms governing gene expression regulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Carcinoma Hepatocelular / Epigénesis Genética / Análisis de la Célula Individual / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Clin Transl Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Carcinoma Hepatocelular / Epigénesis Genética / Análisis de la Célula Individual / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Clin Transl Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos