Single-cell transcriptomic analysis of development and involution of human thymic stroma

doi:10.3969/j.issn.1674-8115.2021.07.004

Abstract

Abstract: Objective

·To explore the transcriptomic dynamics of human thymic stroma cells across different developmental stages.

Methods

·The single-cell transcriptome datasets of human thymus were downloaded from ArrayExpress (E-MATB-8581). The cellular maps of thymic stroma cells across different developmental stages were analyzed based on protein-protein interaction. The differentially expressed genes of fetal, infant and adult stages were calculated. The cell state alternation across different developmental stages was predicted based on functional enrichment analysis.

Results

·The transcriptomic dynamics of thymic epithelial cells (TEC), endothelial cells (Endo) and fibroblasts (Fb) were more remarkable compared with dendritic cells. In adult thymus, there was decline of antigen presenting function and down-regulation of major histocompatibility complex (MHC) class Ⅱ genes in medullary TEC type Ⅰ cells. The fibroblasts enriched functions related to antigen recognition, differentiation and activation of T cells in postnatal thymus. The up-regulated genes of thymic Endo enriched functions such as extracellular matrix during fetal and infant stages, while up-regulated MHC genes and enriched pathways associated with antigen presenting in adult thymus.

Conclusion

·Bioinformatics analysis revealed that mTEC, Fb and Endo were the susceptible stroma cell types in response to thymic development and senescence. The involution of human thymus may affect the negative selection of T cell differentiation mostly.

Key words: thymic stroma, development, negative selection, single-cell RNA-sequencing, gene expression

CLC Number:

R714.51

Yu-chen LI, Li-lian BAI, He-feng HUANG, Xin-mei LIU. Single-cell transcriptomic analysis of development and involution of human thymic stroma[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(7): 865-875.

Figures/Tables 8

Fig 1 UMAP plots of human thymic stroma cells

Fig 2 The KEGG pathway analysis of differentially expressed genes of human cTECs

Fig 3 KEGG pathway analysis of differentially expressed genes of human mTECs

Fig 4 KEGG pathway analysis of differentially expressed genes of human thymic DCs

Fig 5 Differential expression of HLA genes in human thymic APCs

Fig 6 Differentially expressed genes of human thymic Fb1 and Fb2 across development stages

Fig 7 KEGG pathway analysis of differentially expressed genes of human thymic Fb1 and Fb2

Fig 8 Differentially expressed genes of human thymic Endo across development stages

TrendMD

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