Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity.

Cell
Authors
Keywords
Abstract

Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or differentiated in vitro under either pathogenic or non-pathogenic polarization conditions. Computational analysis relates a spectrum of cellular states in vivo to in-vitro-differentiated Th17 cells and unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four new genes: Gpr65, Plzp, Toso, and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity and can identify targets for selective suppression of pathogenic Th17 cells while potentially sparing non-pathogenic tissue-protective ones.

Year of Publication
2015
Journal
Cell
Volume
163
Issue
6
Pages
1400-12
Date Published
2015 Dec 03
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2015.11.009
PubMed ID
26607794
PubMed Central ID
PMC4671824
Links
Grant list
R01 NS030843 / NS / NINDS NIH HHS / United States
R00 AI110649 / AI / NIAID NIH HHS / United States
NS030843 / NS / NINDS NIH HHS / United States
AI039671 / AI / NIAID NIH HHS / United States
P01 AI056299 / AI / NIAID NIH HHS / United States
F32 HD075541 / HD / NICHD NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
P01 NS076410 / NS / NINDS NIH HHS / United States
P01 AI039671 / AI / NIAID NIH HHS / United States
R37 NS030843 / NS / NINDS NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
4R00AI110649 / AI / NIAID NIH HHS / United States
AI056299 / AI / NIAID NIH HHS / United States
R29 NS030843 / NS / NINDS NIH HHS / United States
NS076410 / NS / NINDS NIH HHS / United States