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An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development.
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- Author(s): Chopp LB;Chopp LB;Chopp LB; Gopalan V; Gopalan V; Ciucci T; Ciucci T; Ruchinskas A; Ruchinskas A; Rae Z; Rae Z; Lagarde M; Lagarde M; Gao Y; Gao Y; Li C; Li C; Bosticardo M; Bosticardo M; Pala F; Pala F; Livak F; Livak F; Kelly MC; Kelly MC; Hannenhalli S; Hannenhalli S; Bosselut R; Bosselut R
- Source:
Immunity [Immunity] 2020 Dec 15; Vol. 53 (6), pp. 1182-1201.e8. Date of Electronic Publication: 2020 Nov 25.- Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S.- Language:
English - Source:
- Additional Information
- Source: Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE
- Publication Information: Publication: Cambridge, MA : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1994- - Subject Terms: Cell Differentiation/*immunology ; Cell Lineage/*immunology ; T-Lymphocyte Subsets/*immunology ; Thymocytes/*immunology; Animals ; Antigen Presentation/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Epigenome ; Gene Expression Regulation ; Gene Regulatory Networks ; Histocompatibility Antigens/genetics ; Histocompatibility Antigens/immunology ; Histocompatibility Antigens/metabolism ; Humans ; Mice ; T-Lymphocyte Subsets/metabolism ; Thymocytes/metabolism ; Thymus Gland/immunology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptome
- Abstract: αβ lineage T cells, most of which are CD4 + or CD8 + and recognize MHC I- or MHC II-presented antigens, are essential for immune responses and develop from CD4 + CD8 + thymocytes. The absence of in vitro models and the heterogeneity of αβ thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human αβ thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4 + and CD8 + lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. Through computational analysis of single-cell data and binding sites for the CD4 + -lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4 + - or CD8 + -lineage differentiation, and with expression of Thpok or of the CD8 + -lineage factor Runx3. Our findings provide insight into the mechanisms of CD4 + and CD8 + T cell differentiation and a foundation for mechanistic investigations of αβ T cell development.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Published by Elsevier Inc.) - Comments: Comment in: Immunity. 2020 Dec 15;53(6):1126-1128. doi: 10.1016/j.immuni.2020.11.014. (PMID: 33326761)
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Eur J Immunol. 1993 Mar;23(3):739-46. (PMID: 8095460) - Grant Information: HHSN261200800001C United States CA NCI NIH HHS; HHSN261200800001E United States CA NCI NIH HHS; Z99 CA999999 United States ImNIH Intramural NIH HHS
- Contributed Indexing: Keywords: CD4 T cells; CD8 T cells; Gene regulatory networks; Human thymus; T cell development; Thpok; Transcriptional regulation; single-cell ATACseq; single-cell RNAseq; thymic selection
- Accession Number: 0 (Histocompatibility Antigens)
0 (Th-POK protein, mouse)
0 (Transcription Factors) - Publication Date: Date Created: 20201126 Date Completed: 20210521 Latest Revision: 20240615
- Publication Date: 20240615
- Accession Number: PMC8641659
- Accession Number: 10.1016/j.immuni.2020.10.024
- Accession Number: 33242395
- Source:
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