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Series GSE151408 Query DataSets for GSE151408
Status Public on Aug 13, 2020
Title Erythrophagocytosis drives anti-inflammatory programming of liver macrophages (ATAC-seq)
Organism Mus musculus
Experiment type Genome binding/occupancy 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. Mapping transposase-accessible chromatin in single cells using sequencing (scATAC-seq) suggested NFE2L2/NRF2 as a critical driver of anti-inflammatory erythrophagocytes in the livers of hemolytic mice and heme-suppression of the inflammatory response was abolished in macrophages from Nfe2l2/Nrf2-deficient animals. 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-cell ATAC(10x genomics).
 
Contributor(s) Pfefferlé M, Ingoglia G, Vallelian F, Schaer D
Citation(s) 32663195
Submission date May 28, 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)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (2)
GSM4577497 Macrophages Nucleus WT
GSM4577498 Macrophages Nucleus SPTA
This SubSeries is part of SuperSeries:
GSE145244 Erythrophagocytosis drives anti-inflammatory programming of liver macrophages
Relations
BioProject PRJNA635691
SRA SRP265162

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE151408_filtered_peak_bc_matrix.h5 18.7 Mb (ftp)(http) H5
GSE151408_filtered_tf_bc_matrix.h5 1.0 Mb (ftp)(http) H5
GSE151408_fragments.tsv.gz 358.8 Mb (ftp)(http) TSV
GSE151408_fragments.tsv.gz.tbi.gz 542.3 Kb (ftp)(http) TBI
GSE151408_macATACwithmotifenriched.rds.gz 183.5 Mb (ftp)(http) RDS
GSE151408_singlecell.csv.gz 2.0 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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