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| Status |
Public on Aug 22, 2020 |
| Title |
Single-Cell RNA Sequencing Uncovers Heterogenous Transcriptional Signatures in Macrophages during Efferocytosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Efferocytosis triggers cellular reprogramming, including the induction of mRNA transcripts which encode anti-inflammatory cytokines that promote inflammation resolution. Our current understanding of this transcriptional response is largely informed from analysis of bulk phagocyte populations; however, this precludes the resolution of heterogeneity between individual macrophages and macrophage subsets. Moreover, phagocytes may contain so called “passenger” transcripts that originate from engulfed apoptotic bodies, thus obscuring the true transcriptional reprogramming of the phagocyte. To define the transcriptional diversity during efferocytosis, we utilized single-cell mRNA sequencing after co-cultivating macrophages with apoptotic cells. Importantly, transcriptomic analyses were performed after validating the disappearance of apoptotic cell-derived RNA sequences. Our findings reveal new heterogeneity of the efferocytic response at a single-cell resolution, particularly evident between F4/80+ MHCIILO and F4/80- MHCIIHI macrophage sub-populations. After exposure to apoptotic cells, the F4/80+ MHCIILO subset significantly induced pathways associated with tissue and cellular homeostasis, while the F4/80- MHCIIHI subset downregulated these putative signaling axes. Ablation of a canonical efferocytosis receptor, MerTK, blunted efferocytic signatures and led to the escalation of cell death-associated transcriptional signatures in F4/80+ MHCIILO macrophages. Taken together, our results newly elucidate the heterogenous transcriptional response of single-cell peritoneal macrophages after exposure to apoptotic cells.
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| Overall design |
Examination of efferocytosis at three timepoints between two genotypes of primary macrophages.
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| Contributor(s) |
Lantz CW, Radmanesh B, Liu E, Thorp EB, Lin J |
| Citation(s) |
32868786 |
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| Submission date |
Aug 13, 2020 |
| Last update date |
Sep 08, 2020 |
| Contact name |
Behram Sarosh Radmanesh |
| E-mail(s) |
behram.radmanesh@northwestern.edu
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| Organization name |
Northwestern University
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| Street address |
633 Clark St
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| City |
Evanston |
| State/province |
IL |
| ZIP/Postal code |
60208 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA658604 |
| SRA |
SRP278420 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156234_aggregated_raw_counts.tsv.gz |
15.8 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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