Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq

© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH..

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 5 vom: 01. Feb., Seite e2304755

Sprache:

Englisch

Beteiligte Personen:

Chen, Haide [VerfasserIn]
Fang, Xiunan [VerfasserIn]
Shao, Jikai [VerfasserIn]
Zhang, Qi [VerfasserIn]
Xu, Liwei [VerfasserIn]
Chen, Jiaye [VerfasserIn]
Mei, Yuqing [VerfasserIn]
Jiang, Mengmeng [VerfasserIn]
Wang, Yuting [VerfasserIn]
Li, Zhouyang [VerfasserIn]
Chen, Zihang [VerfasserIn]
Chen, Yang [VerfasserIn]
Yu, Chengxuan [VerfasserIn]
Ma, Lifeng [VerfasserIn]
Zhang, Peijing [VerfasserIn]
Zhang, Tianyu [VerfasserIn]
Liao, Yuan [VerfasserIn]
Lv, Yuexiao [VerfasserIn]
Wang, Xueyi [VerfasserIn]
Yang, Lei [VerfasserIn]
Fu, Yuting [VerfasserIn]
Chen, Daobao [VerfasserIn]
Jiang, Liming [VerfasserIn]
Yan, Feng [VerfasserIn]
Lu, Wei [VerfasserIn]
Chen, Gao [VerfasserIn]
Shen, Huahao [VerfasserIn]
Wang, Jingjing [VerfasserIn]
Wang, Changchun [VerfasserIn]
Liang, Tingbo [VerfasserIn]
Han, Xiaoping [VerfasserIn]
Wang, Yongcheng [VerfasserIn]
Guo, Guoji [VerfasserIn]

Links:

Volltext

Themen:

63231-63-0
Full-length RNA
High-throughput and high-sensitivity
Journal Article
Pan-cancer
RNA
Single-nucleus RNA sequencing
Total RNA

Anmerkungen:

Date Completed 05.02.2024

Date Revised 05.02.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/advs.202304755

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM365021512