Single-cell Transcriptional Profiling of Splenic Fibroblasts Reveals Subset-specific Innate Immune Signatures in Homeostasis and During Viral Infection

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Dec 3

PMID 34857864

Citations 9

Authors

Joern Pezoldt

Carolin Wiechers

Florian Erhard

Ulfert Rand

Tanja Bulat

Michael Beckstette

Andrea Brendolan

Jochen Huehn

Ulrich Kalinke

Mathias Mueller

Birgit Strobl

Bart Deplancke

Luka Cicin-Sain

Katarzyna M Sitnik

Affiliations

Soon will be listed here.

Abstract

Our understanding of the composition and functions of splenic stromal cells remains incomplete. Here, based on analysis of over 20,000 single cell transcriptomes of splenic fibroblasts, we characterized the phenotypic and functional heterogeneity of these cells in healthy state and during virus infection. We describe eleven transcriptionally distinct fibroblastic cell clusters, reassuring known subsets and revealing yet unascertained heterogeneity amongst fibroblasts occupying diverse splenic niches. We further identify striking differences in innate immune signatures of distinct stromal compartments in vivo. Compared to other fibroblasts and to endothelial cells, Ly6C fibroblasts of the red pulp were selectively endowed with enhanced interferon-stimulated gene expression in homeostasis, upon systemic interferon stimulation and during virus infection in vivo. Collectively, we provide an updated map of fibroblastic cell diversity in the spleen that suggests a specialized innate immune function for splenic red pulp fibroblasts.

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