Single-Cell RNA Sequencing Uncovers Heterogenous Transcriptional Signatures in Macrophages during Efferocytosis
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ABSTRACT:
PROVIDER: PRJNA658604 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12494000_1.fastq.gz | Fastqsanger.gz | |||
| SRR12494000_2.fastq.gz | Fastqsanger.gz | |||
| SRR12494001_1.fastq.gz | Fastqsanger.gz | |||
| SRR12494001_2.fastq.gz | Fastqsanger.gz | |||
| SRR12494002_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2020-08-22 | GSE156234 | GEO
Project description: Not available
| S-EPMC7459098 | biostudies-literature
Project description:Fever, a cardinal sign of inflammation, has been shown to modulate macrophage functions. Here, we wonder whether fever affects macrophage efferocytosis. This process is critical for the resolution of inflammation and the return to homeostasis with the reprogramming of macrophages toward a pro-resolving phenotype. Using primary mouse bone marrow-derived macrophages (BMDM) stimulated by LPS and IFN-γ (M1-like BMDM), we first validated that exposure to febrile-range temperature (39.5°C) induced a heat shock protein response. This was done by RNA sequencing (RNAseq), quantitative RT-PCR (RT-qPCR), and intracellular flow cytometry (FC). Then, we observed that febrile-range temperature decreased pro-inflammatory macrophage efferocytosis assessed by two different FC-based assays and by IncuCyte® live-cell imaging. This reduced efferocytic capacity of macrophages exposed to febrile-range temperature resulted from a decrease capacity to interact with apoptotic cells and to internalise these dying cells. This real-time image-based efferocytosis assay showed also that the heat reduced cell motility of macrophages in response to apoptotic cells. In our RNAseq dataset, we found an upregulation of the Adam17 gene and confirmed this increase by RT-qPCR analysis. Since this gene encodes a protease shedding the efferocytic receptor Mer, we determined Mer expression by FC and soluble Mer in the culture supernatants by ELISA. Febrile-range hyperthermia induced the cleavage of Mer from the cell surface of pro-inflammatory macrophages. Overall, decreased efferocytosis induced by fever-range hyperthermia may result from reduced Mer expression. This suggests that fever, by acting on Mer expression, decreases the efferocytic capacity of macrophages to prolong the pro-inflammatory state.
2025-12-19 | E-MTAB-14408 | biostudies-arrayexpress
Project description:Poor wound healing due to dysregulated tissue repair responses can exacerbate and prolong disease. Successful tissue repair is critically dependent on the timely clearance of apoptotic cells by macrophages in a process termed efferocytosis. Mechanisms and factors that link these two fundamental processes are therefore of great interest. Herein, we observed that a subset of 12-lipoxygenase (ALOX12)-expressing macrophages upregulate the production of host protective autacoids termed maresin conjugates in tissue regeneration (MCTR) during efferocytosis. MCTRs in turn play autocrine and paracrine functions in enhancing the ability of both ALOX12-positive and surrounding ALOX12-negative macrophages to uptake apoptotic cells. These effects of ALOX12-positive macrophages and MCTRs in regulating apoptotic cells clearance was also observed at sites of high apoptotic cell burden in mouse and flatworm models, as the formation of these mediators was upregulated and abrogation of related ALOX activity in mice reduced the ability of macrophages to clear apoptotic cells. Furthermore, add-back of MCTRs rapidly enhanced the efferocytosis capability of macrophages in mice and planarian flatworms. Mechanistic studies in macrophages revealed that MCTRs modulated Rac1 signalling and glycolytic metabolism, two pathways crucial for effective efferocytosis, and enhanced efferocytosis-induced WNT ligand production. Inhibition of Rac1 abrogated the ability of MCTRs to enhance glucose uptake and efferocytosis in vitro, while inhibiting either Rac1, glycolysis, or WNT ligand production prevented MCTR-mediated enhancement of apoptotic cell clearance and tissue regeneration. Taken together, our findings identify a central role for ALOX12-expressing macrophages in the regulation of efferocytosis and tissue repair via the local formation of MCTRs.
2023-12-12 | PXD038390 | Pride
Project description:Macrophages remove apoptotic cells by efferocytosis during immune-surveillance and in the tumor microenvironment (TME). However, the gradual molecular and epigenetic consequences of efferocytosis on the single macrophage are not thoroughly elucidated. Here we introduce Effero-seq, an approach that captures single-cell transcriptomic changes coupled with lysosomal acidification tracked by pHrodo, thus enabling the dissection of molecular dynamics over time following engulfment. Using apoptotic pHrodo-labeled cells as cargo, we defined the effero-score, a gene program gradually upregulated correlatively with pHrodo intensity. In a murine melanoma model, we found that efferocytosis induces a pro-angiogenic function in macrophages with spatial proximity to vascular niches. Moreover, efferocytosis reprograms chromatin accessibility, leading to attenuated macrophage response to IFNγ. In human uveal melanoma, expression of the effero-score is correlated with poor survival. Effero-seq sheds light on the molecular reprogramming induced by efferocytosis in the TME, opening new avenues for understanding macrophage function and developing targeted treatments.
2026-06-05 | GSE300757 | GEO
Project description:Tumor cell efferocytosis in monocyte derived macrophages
| PRJNA763980 | ENA
Project description:Macrophages are metabolically heterogenous within the tumor microenvironment
| PRJNA779399 | ENA
Project description:Macrophages remove apoptotic cells by efferocytosis during immune-surveillance and in the tumor microenvironment (TME). However, the gradual molecular and epigenetic consequences of efferocytosis on the single macrophage are not thoroughly elucidated. Here we introduce Effero-seq, an approach that captures single-cell transcriptomic changes coupled with lysosomal acidification tracked by pHrodo, thus enabling the dissection of molecular dynamics over time following engulfment. Using apoptotic pHrodo-labeled cells as cargo, we defined the effero-score, a gene program gradually upregulated correlatively with pHrodo intensity. In a murine melanoma model, we found that efferocytosis induces a pro-angiogenic function in macrophages with spatial proximity to vascular niches. Moreover, efferocytosis reprograms chromatin accessibility, leading to attenuated macrophage response to IFNγ. In human uveal melanoma, expression of the effero-score is correlated with poor survival. Effero-seq sheds light on the molecular reprogramming induced by efferocytosis in the TME, opening new avenues for understanding macrophage function and developing targeted treatments.
2026-06-05 | GSE306916 | GEO
Project description:Inflammation is a physiopathological process triggered by infection or tissue damage. Immune system initiates coordinated sequential steps in response to these danger signals. Once the threat has been contained inflammation has to be subsequently shut down. Inflammation resolution is initiated by the reprogramming of pro-inflammatory macrophages toward a pro-resolving profile. This reprogramming is induced in particular by the non-phlogistic engulfment of apoptotic cells, mostly apoptotic neutrophils, a process called efferocytosis. As a matter of fact, macrophages are an essential linchpin regulating both inflammation triggering and sustaining and inflammation resolution. This duality can be achieved through the tremendous plasticity of these innate immune cells. Indeed, depending on microenvironmental signals (cytokines, efferocytosis, growth factors…) macrophages can adopt numerous diverse and sometimes antagonistic phenotypes. The mechanisms governing these transitions remain relatively scattered especially in human. With this project we propose to explore the mechanisms involved in human macrophage reprogramming toward a pro-resolving profile after efferocytosis. The stakes are high due to the estimated prevalence of chronic inflammatory diseases in Western society is 5 to 7%. Chronic inflammation is a burden to patient due to life-long debilitating illness and increased mortality and is also a burden to society due to high costs for therapy and care. Finding new therapies to limit chronic inflammation establishment and persistence is thus a highly valuable goal.
2021-12-01 | E-MTAB-8885 | biostudies-arrayexpress
Project description:Defects in apoptotic cell clearance, or efferocytosis, can cause inflammatory diseases and prevent tissue repair due in part, to a key role of efferocytosis in inducing a pro-repair transcriptional program in phagocytic cells like macrophages. While the cellular machinery and metabolic pathways involved in efferocytosis have been characterized, the precise efferocytic response of macrophages is dependent on the identity and macromolecular cues of apoptotic cells, and the complex tissue microenvironment in which efferocytosis occurs. Here, we find that macrophages undergoing active efferocytosis in mid-stage mouse skin wounds in vivo display a pro-repair gene program, while efferocytosis of apoptotic skin fibroblasts in vitro induces an immature/inflammatory transcription response. These data provide a resource for understanding how the skin wound niche influences macrophage efferocytosis and will be useful for future investigations that define the role of efferocytosis during tissue repair
2024-08-06 | GSE273754 | GEO