Dissecting cellular crosstalk by sequencing physically interacting cells.
Amir GiladiMerav CohenChiara MedagliaYael BaranBaoguo LiMor ZadaPierre BostRonnie Blecher-GonenTomer-Meir SalameJohannes U MayerEyal DavidFranca RoncheseAmos TanayBjørt K KragesteenPublished in: Nature biotechnology (2020)
Crosstalk between neighboring cells underlies many biological processes, including cell signaling, proliferation and differentiation. Current single-cell genomic technologies profile each cell separately after tissue dissociation, losing information on cell-cell interactions. In the present study, we present an approach for sequencing physically interacting cells (PIC-seq), which combines cell sorting of physically interacting cells (PICs) with single-cell RNA-sequencing. Using computational modeling, PIC-seq systematically maps in situ cellular interactions and characterizes their molecular crosstalk. We apply PIC-seq to interrogate diverse interactions including immune-epithelial PICs in neonatal murine lungs. Focusing on interactions between T cells and dendritic cells (DCs) in vitro and in vivo, we map T cell-DC interaction preferences, and discover regulatory T cells as a major T cell subtype interacting with DCs in mouse draining lymph nodes. Analysis of T cell-DC pairs reveals an interaction-specific program between pathogen-presenting migratory DCs and T cells. PIC-seq provides a direct and broadly applicable technology to characterize intercellular interaction-specific pathways at high resolution.
Keyphrases
- single cell
- rna seq
- dendritic cells
- induced apoptosis
- high throughput
- regulatory t cells
- cell cycle arrest
- lymph node
- high resolution
- cell therapy
- cell death
- healthcare
- stem cells
- signaling pathway
- early stage
- mass spectrometry
- endoplasmic reticulum stress
- oxidative stress
- quality improvement
- bone marrow
- mesenchymal stem cells
- copy number
- cell proliferation
- high speed