Single-cell RNA-seq and chromatin accessibility profiling decipher the heterogeneity of mouse γδ T cells

• 作者: Zhenhua Li Quanli Yang Xin Tang Yiming Chen Shanshan Wang Xiaojie Qi Yawen Zhang Zonghua Liu Jing Luo Hui Liu Yongbing Ba Lianxia Guo Baojian Wu Fang Huang Guangchao Cao Zhinan Yin
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2022,（4）
• 所属期刊栏目: ARTICLES
• 页码范围: 408-426
• 页数: 19页
• 语种: 英文

摘要

The distinct characteristics of γδ T cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity of γδ T cells across tissues remains unclear.By combining transcriptional and chromatin analyses with a truly unbiased fashion,we constructed a single-cell transcriptome and chromatin accessibility landscape of mouse γδ T cells in the lymph,spleen,and thymus.We also revealed the heterogeneity of γδ T1 and γδ T17 cells across these tissues and inferred their potential regulatory mechanisms.In the thymus,we reconstructed the developmental trajectory and gained further insights into the signature genes from the mature stage,intermediate stage,and immature stage of γδ T cells on the basis of single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing data.Notably,a novel Gzma+ γδ T cell subset was identified with immature properties and only localized to the thymus.Finally,NR1D1,a cir-cadian transcription factor (TF),was validated as a key and negative regulator of γδ T17 cell differentia-tion by performing a combined analysis of TF motif enrichment,regulon enrichment,and Nr1d1 knockout mice.In summary,our data represent a comprehensive mapping on the transcriptome and chromatin accessibility dynamics of mouse γδ T cells,providing a valuable resource and reference for future studies on γδ T cells.