The distinct characteristics ofγδT cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity ofγδT cells across tissues remains unc...The distinct characteristics ofγδT cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity ofγδT 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 mouseγδT cells in the lymph,spleen,and thymus.We also revealed the heterogeneity ofγδT1 andγδT17 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 ofγδT cells on the basis of single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing data.Notably,a novel Gzma^(+)γδT cell subset was identified with immature properties and only localized to the thymus.Finally,NR1 D1,a circadian transcription factor(TF),was validated as a key and negative regulator ofγδT17 cell differentiation by performing a combined analysis of TF motif enrichment,regulon enrichment,and Nr1 d1 knockout mice.In summary,our data represent a comprehensive mapping on the transcriptome and chromatin accessibility dynamics of mouseγδT cells,providing a valuable resource and reference for future studies onγδT cells.展开更多
基金supported by the National Natural Science Foundation of China(31830021,32030036,32000615,and 32100695)the National Key Research and Development Program of China(2020YFA0803502)+2 种基金the 111 Project(B16021)China Postdoctoral Science Foundation(2020M683180,2019M663374,and 2020T130251)Guangdong Basic and Applied Basic Research Foundation(2020A1515111045 and 2020A1515111081)。
文摘The distinct characteristics ofγδT cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity ofγδT 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 mouseγδT cells in the lymph,spleen,and thymus.We also revealed the heterogeneity ofγδT1 andγδT17 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 ofγδT cells on the basis of single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing data.Notably,a novel Gzma^(+)γδT cell subset was identified with immature properties and only localized to the thymus.Finally,NR1 D1,a circadian transcription factor(TF),was validated as a key and negative regulator ofγδT17 cell differentiation by performing a combined analysis of TF motif enrichment,regulon enrichment,and Nr1 d1 knockout mice.In summary,our data represent a comprehensive mapping on the transcriptome and chromatin accessibility dynamics of mouseγδT cells,providing a valuable resource and reference for future studies onγδT cells.
