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Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation
Denise Tischner, Myriam Grimm, Harmandeep Kaur, Daniel Staudenraus, Jorge Carvalho, Mario Looso, Stefan Günther, Florian Wanke, Sonja Moos, Nelly Siller, Johanna Breuer, Nicholas Schwab, Frauke Zipp, Ari Waisman, Florian C. Kurschus, Stefan Offermanns, Nina Wettschureck
Denise Tischner, Myriam Grimm, Harmandeep Kaur, Daniel Staudenraus, Jorge Carvalho, Mario Looso, Stefan Günther, Florian Wanke, Sonja Moos, Nelly Siller, Johanna Breuer, Nicholas Schwab, Frauke Zipp, Ari Waisman, Florian C. Kurschus, Stefan Offermanns, Nina Wettschureck
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Research Article Immunology

Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation

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Abstract

GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord–infiltrating CD4 T cells, macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1P1, and LPHN2 as examples, we show how this information can be used to develop new strategies for the functional modulation of Th17 cells and activated endothelial cells. Taken together, single-cell GPCR expression analysis identifies functionally relevant subpopulations with specific GPCR repertoires and provides a basis for the development of new therapeutic strategies in immune disorders.

Authors

Denise Tischner, Myriam Grimm, Harmandeep Kaur, Daniel Staudenraus, Jorge Carvalho, Mario Looso, Stefan Günther, Florian Wanke, Sonja Moos, Nelly Siller, Johanna Breuer, Nicholas Schwab, Frauke Zipp, Ari Waisman, Florian C. Kurschus, Stefan Offermanns, Nina Wettschureck

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Figure 5

Single-cell GPCR expression in splenic monocytes versus spinal cord–infiltrating CD11b-positive cells (CD11b_sc).

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Single-cell GPCR expression in splenic monocytes versus spinal cord–infi...
(A) Heat map of GPCR expression in CD11b+Ly6Chigh monocytes and CD11b_sc cells (monocytes: 42 cells from 2 mice; CD11b_sc: 98 cells from 6 mice); horizontal bars on the right side visualize expression frequency (%). (B) Number of GPCRs expressed in individual monocytes and CD11b_sc cells. (C) Number of GPCRs expressed in monocytes and in vitro–differentiated M1- or M2-polarized BM-derived macrophages (BMDM_M1: 31 cells; BMDM_M2: 38 cells). (D) T-SNE map representation of transcriptome similarities of in vitro–differentiated macrophages (BMDM_M1, BMDM_M2) or in vivo–differentiated myeloid cells (Cd11b_sc). K-means cluster assignment is color-coded; cell type is indicated by symbol.

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