GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE179362 Query DataSets for GSE179362
Status Public on Jan 25, 2022
Title Heme exposure shifts shifts myeloid differentiation in bone marrow derived mixed cell cultures.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Heme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Here, we performed single-cell RNA sequencing with RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation trajectories of cells towards antioxidant, iron-recycling macrophages at the expense of dendritic cells, as these cells were selectively deficient in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning how hemolytic stress may provoke hyposplenism-related secondary immunodeficiency, which is a critical determinant of mortality in patients with genetic hemolytic anemias.
Overall design M-CSF- and GM-CSF-supplemented BM cell cultures were stimulated with heme (300μM) or albumin (control) on day 3. On day 7, the cells were harvested, tagged with DNA-barcoded antibodies, and pooled into a single scRNA-seq sample for sequencing.
Contributor(s) Buzzi RM, Pfefferlé M, Schaer DJ, Vallelian F
Citation(s) 35031770
Submission date Jul 02, 2021
Last update date Jan 26, 2022
Contact name Raphael Matthias Buzzi
Organization name Universitätsspital and University of Zurich
Department Division of Internal Medicine
Street address Rämistrasse 100
City Zürich
ZIP/Postal code 8091
Country Switzerland
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (1)
GSM5416214 Multiplexed BM-derived cell culture experiment
This SubSeries is part of SuperSeries:
GSE179365 Heme-activated Nrf2 signaling skews fate trajectories of bone marrow cells from dendritic cells towards macrophages
BioProject PRJNA743342
SRA SRP326707

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
GSE179362_RAW.tar 269.9 Mb (http)(custom) TAR (of H5AD, MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap