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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 14, 2024 |
| Title |
Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodelling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodelling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodelling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.
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| Overall design |
We studied leukocytes from hearts in Csf1r∆FIRE mice in baseline conditions and 2 days after ischemia/reperfusion injury. At the 2 specific timepoints leukocytes were harvested from the heart using MACS as well as FACS sorting strategies for CD45+ cells.
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| Contributor(s) |
Joppich M, Weinberger T, Schulz C |
| Citation(s) |
38775664 |
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| Submission date |
Apr 09, 2024 |
| Last update date |
Jun 05, 2024 |
| Contact name |
Markus Joppich |
| E-mail(s) |
joppich@bio.ifi.lmu.de
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| Organization name |
LMU Munich
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| Department |
Department of Informatics
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| Lab |
LFE Bioinformatik
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| Street address |
Amalienstr. 17
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| City |
Munich |
| State/province |
Bavaria |
| ZIP/Postal code |
80333 |
| Country |
Germany |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (10)
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| GSM8194265 |
MI d2, Csf1r∆FIRE/+, FIRE_IF_WT R2 |
| GSM8194266 |
Baseline, Csf1r∆FIRE/+, FIRE_NI_CTRL R1 |
| GSM8194267 |
Baseline, Csf1r∆FIRE/+, FIRE_NI_CTRL R2 |
| GSM8194268 |
Baseline, Csf1r∆FIRE/+, FIRE_NI_CTRL R3 |
| GSM8194269 |
Baseline, Csf1r∆FIRE/∆FIRE , FIRE_NI_KO R1 |
| GSM8194270 |
Baseline, Csf1r∆FIRE/∆FIRE, FIRE_NI_KO R2 |
| GSM8194271 |
Baseline, Csf1r∆FIRE/∆FIRE, FIRE_NI_KO R3 |
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| Relations |
| BioProject |
PRJNA1098025 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE263545_RAW.tar |
467.1 Mb |
(http)(custom) |
TAR (of H5) |
| GSE263545_heart1_raw_feature_bc_matrix.tar.gz |
58.8 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
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