Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis
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ABSTRACT:
PROVIDER: PRJNA631011 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11729315_1.fastq.gz | Fastqsanger.gz | |||
| SRR11729315_2.fastq.gz | Fastqsanger.gz | |||
| SRR11729316_1.fastq.gz | Fastqsanger.gz | |||
| SRR11729316_2.fastq.gz | Fastqsanger.gz | |||
| SRR11729317_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Traditionally, the transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed by two largely exclusive types of technologies: single-cell RNA-sequencing (scRNA-seq) and antibody-based cytometry. Here we present a multi-omics approach allowing the simultaneous targeted quantification of mRNA and protein expression in single-cells and investigate its performance to dissect the heterogeneity of human immune cell populations. Methods: We have quantified the single-cell expression of 397 genes at the mRNA level and up to 68 proteins using oligo-conjugated antibodies (AbSeq) in 43,656 primary CD4+ T cells isolated from blood and 31,907 CD45+ cells isolated from blood and matched duodenal biopsies. We explored the sensitivity of this targeted scRNA-seq approach to dissect the heterogeneity of human immune cell populations and identify trajectories of functional T-cell differentiation. Results: We provide a high-resolution map of human primary CD4+ T cells, and identify precise trajectories of Th1, Th17 and regulatory T-cell (Treg) differentiation in blood and tissue. The sensitivity provided by this multi-omics approach identified the expression of the B7 molecules CD80 and CD86 on the surface of CD4+ Tregs, and we further demonstrated that B7 expression has the potential to identify recently activated T cells in circulation. Moreover, we identified a rare subset of CCR9+ T cells in blood with gut-homing properties and expression of several immunomodulatory receptors, suggestive of a regulatory function at barrier sites. Conclusions: This transcriptomic and proteomic hybrid technology provides a cost-effective solution to dissect the heterogeneity of immune cell populations, including more precise and detailed descriptions of the differentiation and activation of circulating and tissue-resident cells in response to therapies and in stratification of patients.
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Project description:BackgroundTraditionally, the transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed by two largely exclusive types of technologies: single-cell RNA sequencing (scRNA-seq) and antibody-based cytometry. Here, we present a multi-omics approach allowing the simultaneous targeted quantification of mRNA and protein expression in single cells and investigate its performance to dissect the heterogeneity of human immune cell populations.MethodsWe have quantified the single-cell expression of 397 genes at the mRNA level and up to 68 proteins using oligo-conjugated antibodies (AbSeq) in 43,656 primary CD4+ T cells isolated from the blood and 31,907 CD45+ cells isolated from the blood and matched duodenal biopsies. We explored the sensitivity of this targeted scRNA-seq approach to dissect the heterogeneity of human immune cell populations and identify trajectories of functional T cell differentiation.ResultsWe provide a high-resolution map of human primary CD4+ T cells and identify precise trajectories of Th1, Th17 and regulatory T cell (Treg) differentiation in the blood and tissue. The sensitivity provided by this multi-omics approach identified the expression of the B7 molecules CD80 and CD86 on the surface of CD4+ Tregs, and we further demonstrated that B7 expression has the potential to identify recently activated T cells in circulation. Moreover, we identified a rare subset of CCR9+ T cells in the blood with tissue-homing properties and expression of several immune checkpoint molecules, suggestive of a regulatory function.ConclusionsThe transcriptomic and proteomic hybrid technology described in this study provides a cost-effective solution to dissect the heterogeneity of immune cell populations at extremely high resolution. Unexpectedly, CD80 and CD86, normally expressed on antigen-presenting cells, were detected on a subset of activated Tregs, indicating a role for these co-stimulatory molecules in regulating the dynamics of CD4+ T cell responses.
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