Universal recording of cell-cell contacts in vivo for interaction-based transcriptomics.
Sandra Nakandakari-HigaMaria C C CanessoSarah WalkerAleksey ChudnovskiyJohanne T JacobsenS Martina ParigiKarol FiedorczukElaine FuchsAngelina M BilateGiulia PasqualDaniel MucidaYuri PritykinGabriel D VictoraPublished in: bioRxiv : the preprint server for biology (2023)
Cellular interactions are essential for tissue organization and functionality. In particular, immune cells rely on direct and usually transient interactions with other immune and non-immune populations to specify and regulate their function. To study these "kiss-and-run" interactions directly in vivo , we previously developed LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts), an approach that uses enzymatic transfer of a labeled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4 + helper T cells and antigen presenting cells, however. Here, we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8 + T cells by dendritic cells, reveal the cellular partners of regulatory T cells in steady state, and identify germinal center (GC)-resident T follicular helper (Tfh) cells based on their ability to interact cognately with GC B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalog of the immune populations that physically interact with intestinal epithelial cells (IECs) and identify a receptor-ligand pair necessary for the interaction between IECs and intraepithelial lymphocytes (IELs). Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell-cell interactions across multiple biological systems.
Keyphrases
- single cell
- regulatory t cells
- dendritic cells
- rna seq
- induced apoptosis
- cell cycle arrest
- cell therapy
- immune response
- physical activity
- high throughput
- cell death
- stem cells
- computed tomography
- mental health
- mesenchymal stem cells
- nitric oxide
- ionic liquid
- public health
- endoplasmic reticulum stress
- case report
- dna methylation
- gene expression
- pi k akt
- bone marrow
- patient safety
- single molecule
- hepatitis c virus
- hiv infected
- protein kinase
- cell adhesion