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Series GSE145241 Query DataSets for GSE145241
Status Public on Aug 13, 2020
Title Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (Single-cell RNA-seq SPTA mac)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Under conditions of erythrolytic stress, which accompanies many disease states, macrophages play key roles in phagocytosing damaged RBCs and preventing the toxic effects of cell-free hemoglobin and heme to maintain homeostasis. Using a genetic mouse model of spherocytosis and single-cell RNA sequencing, we show that erythrolytic stress promotes expansion of a specific macrophage population in the liver (which we named “erythrophagocytes”) expressing high levels of Marco and Hmox1 and low levels of MHC class II related genes with an anti-inflammatory gene expression signature. We confirmed the strong anti-inflammatory function of erythrophagocytes in two models of sterile inflammatory liver disease: anti-CD40 antibody-induced systemic inflammation syndrome with necrotizing hepatitis and diet-induced nonalcoholic fatty liver disease (NAFLD). The unique anti-inflammatory phenotype and function of erythrophagocytes was reproduced in vitro by heme-exposure of mouse macrophages, yielding a transcriptional profile that segregated heme-polarized from classical M1- and M2-polarized cells. The phenotype of anti-inflammatory erythrophagocytes coincided with NFE2L2/NRF2 driven gene expression and was abolished in Nfe2l2/Nrf2-deficient macrophages. Our findings point to a novel pathway that regulates macrophage functions to link RBC homeostasis and heme metabolism with innate immunity.
 
Overall design Liver macrophages from a sph/sph mouse and its littermate wild-type control were isolated using anti-F4/80 antibody coated dynabeads and subjected to droplet-based single-RNA sequencing (10x genomics).
 
Contributor(s) Pfefferlé M, Ingoglia G, Vallelian F, Schaer D
Citation(s) 32663195
Submission date Feb 13, 2020
Last update date Nov 27, 2020
Contact name Marc Pfefferle
E-mail(s) marc.pfefferle@uzh.ch
Organization name University hospital Zürich (USZ)
Street address Wagistrasse 12
City Schlieren
State/province Schweiz
ZIP/Postal code 8952
Country Switzerland
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM4310088 Macrophages WT
GSM4310089 Macrophages SPTA
This SubSeries is part of SuperSeries:
GSE145244 Erythrophagocytosis drives anti-inflammatory programming of liver macrophages
Relations
BioProject PRJNA606505
SRA SRP249274

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Supplementary file Size Download File type/resource
GSE145241_barcodes.tsv.gz 92.7 Kb (ftp)(http) TSV
GSE145241_features.tsv.gz 225.5 Kb (ftp)(http) TSV
GSE145241_matrix.mtx.gz 98.7 Mb (ftp)(http) MTX
GSE145241_sce-SPTAmerged-Final.rds.gz 123.3 Mb (ftp)(http) RDS
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Raw data are available in SRA
Processed data are available on Series record

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