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Series GSE179363 Query DataSets for GSE179363
Status Public on Jan 25, 2022
Title Deviated myeloid differentiation in SCD mice under heme stress I.
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 Single cell suspensions negatively enriched for DCs from a spleen of a SCD and wild-type mouse subjected to droplet-based single-RNA sequencing (10x genomics).
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 (2)
GSM5416215 single cell suspension negatively enriched for DCs from a spleen of a wild-type mouse
GSM5416216 single cell suspension negatively enriched for DCs from a spleen of a SCD mouse
This SubSeries is part of SuperSeries:
GSE179365 Heme-activated Nrf2 signaling skews fate trajectories of bone marrow cells from dendritic cells towards macrophages
BioProject PRJNA743344
SRA SRP326709

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Supplementary file Size Download File type/resource
GSE179363_RAW.tar 204.9 Mb (http)(custom) TAR (of MTX, TSV)
GSE179363_Spleen_negative_selection.h5ad.gz 2.1 Gb (ftp)(http) H5AD
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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