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Publication : Universal recording of cell-cell contacts in vivo for interaction-based transcriptomics.

First Author  Nakandakari-Higa S Year  2023
Journal  bioRxiv PubMed ID  36993443
Mgi Jnum  J:334846 Mgi Id  MGI:7464297
Doi  10.1101/2023.03.16.533003 Citation  Nakandakari-Higa S, et al. (2023) Universal recording of cell-cell contacts in vivo for interaction-based transcriptomics. bioRxiv
abstractText  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.
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