Time-resolved assessment of single-cell protein secretion by sequencing.
Tongjin WuHoward John WomersleyJiehao Ray WangJonathan ScolnickLih Feng CheowPublished in: Nature methods (2023)
Secreted proteins play critical roles in cellular communication. Methods enabling concurrent measurement of cellular protein secretion, phenotypes and transcriptomes are still unavailable. Here we describe time-resolved assessment of protein secretion from single cells by sequencing (TRAPS-seq). Released proteins are trapped onto the cell surface and probed by oligonucleotide-barcoded antibodies before being simultaneously sequenced with transcriptomes in single cells. We demonstrate that TRAPS-seq helps unravel the phenotypic and transcriptional determinants of the secretion of pleiotropic T H 1 cytokines (IFNγ, IL-2 and TNF) in activated T cells. In addition, we show that TRAPS-seq can be used to track the secretion of multiple cytokines over time, uncovering unique molecular signatures that govern the dynamics of single-cell cytokine secretions. Our results revealed that early central memory T cells with CD45RA expression (T CMRA ) are important in both the production and maintenance of polyfunctional cytokines. TRAPS-seq presents a unique tool for seamless integration of secretomics measurements with multi-omics profiling in single cells.
Keyphrases
- single cell
- rna seq
- induced apoptosis
- high throughput
- cell cycle arrest
- rheumatoid arthritis
- binding protein
- protein protein
- genome wide
- radiation therapy
- cell surface
- endoplasmic reticulum stress
- gene expression
- working memory
- dna methylation
- poor prognosis
- amino acid
- cell proliferation
- dendritic cells
- transcription factor
- idiopathic pulmonary fibrosis
- ankylosing spondylitis