A subset of pro-inflammatory spiny mice macrophages promotes a regenerative phenotype in mouse fibroblasts
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA754776 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Macrophages play an essential role in tissue regeneration. However, the ability to dissect the role of macrophages in regeneration from their role in wound healing with scar has been hampered by a lack of comparative systems. In this study, we use a mammalian model of tissue regeneration and scar formation to contrast the role of macrophages in both wound healing paradigms. The African Spiny mouse (A. cahirinus) can regenerate tissue of the external ear pinnae after 4mm biopsy punch. The common lab mouse (M. musculus) forms a scar after the same injury. We test the potential of bone marrow derived macrophages from both species to activate local ear fibroblasts and find macrophages from A. cahirinus are able to induce a matrix turnover phenotype in fibroblasts from both species. We identify growth factors and cytokines specific to macrophages derived from A. cahirinus, and using single cell RNAseq and screening with these factors, we identify populations of macrophages unique to a regenerating injury compared to scar forming injury. Finally we test how macrophage populations change over time in a regenerating injury and how they differ from each stage in a scar forming system
2023-10-23 | GSE182141 | GEO
Project description:A subset of late infiltrating neutrophils have a unique transcriptome of alternative activation associated with their pro-regenerative capacity
| PRJNA824514 | ENA
Project description:Immune stimulation recruits a subset of pro-regenerative macrophages to the retina that promotes axonal regrowth of injured neurons
| PRJNA972278 | ENA
Project description:Purpose: To study the requirement of Osr1 expression for FAP function during skeletal muscle regeneration. Methods: We sequenced total mRNAs isolated from adult FAPs FACS sorted from 3 and 7 day post injured hindlimb skeletal muscle of Ctrl (Osr1flox/+ CAGG Cre+) and Osr1 cKO (Osr1flox/flox CAGG Cre+) mice. Results: Loss of Osr1 leads to pro-fibrotic orientation of FAPs and impairs both FAP-macrophage and FAP-MuSCs communication network resulting in impaired regenerative myogenesis and persistent fibrosis. Conclusions: Osr1 is a key transcriptional regulator of FAP regenerative function protecting FAPs from assuming a detrimental pro-fibrotic and anti-myogenic state.
2023-03-13 | GSE226683 | GEO
Project description:Deoxyhypusine Synthase Promotes a Pro-Inflammatory Macrophage Phenotype
| PRJNA604198 | ENA
Project description:The multifaceted nature of neuroinflammation is highlighted by its ability to both aggravate and promote neuronal health. While in mammals retinal ganglion cells (RGCs) are unable to regenerate following injury, acute inflammation can induce axonal regrowth. However, the nature of the cells, cellular states and signalling pathways that drive this inflammation-induced regeneration have remained elusive. Here, we investigated the functional significance of macrophages during RGC de- and regeneration, by characterizing the inflammatory cascade evoked by optic nerve crush (ONC) injury, with or without local inflammatory stimulation in the vitreous. By combining single-cell RNA sequencing and fate mapping approaches, we elucidated the response of retinal microglia and recruited monocyte-derived macrophages (MDMs) to RGC injury. Importantly, inflammatory stimulation recruited large numbers of MDMs to the retina, which exhibited long-term engraftment and promoted axonal regrowth. Ligand-receptor analysis highlighted a subset of recruited macrophages that exhibited expression of pro-regenerative secreted factors, which were able to promote axon regrowth via paracrine signalling. Our work reveals how inflammation may promote CNS regeneration by modulating innate immune responses, providing a rationale for macrophage-centred strategies for driving neuronal repair following injury and disease.
2023-05-31 | GSE232470 | GEO
Project description:Recent studies using advanced techniques such as single cell RNA sequencing (scRNAseq), high parameter flow cytometry, and proteomics have revealed that neutrophils are more heterogeneous than previously thought. Unique subsets have been identified in the context of bacterial and parasitic infections, cancer and tissue injury and repair. The diversity of subsets that predominate the neutrophil infiltrate in each of these conditions appears dependent on the type of injury and timing of neutrophil involvement in the disease state. We previously described a subpopulation of immature Ly6Glow neutrophils that accumulate in the peritoneal cavity 3 days following intraperitoneal (i.p.) administration of the fungal cell wall extract, zymosan. In contrast, conventional, mature Ly6Ghi neutrophils dominate the peritoneal infiltrate 4 hours following i.p. zymosan injection. The 3 day Ly6Glow, but not 4 hour Ly6Ghi, neutrophils induce neurite outgrowth of explanted neurons in vitro. Furthermore, they drive axon regeneration in the optic nerve (ON) and spinal cord (SC) when adoptively transferred in proximity to the eye after ON crush injury or SC dorsal column transection, respectively. These pro-regenerative effects are mediated in part, by the production of the growth factors insulin-like growth factor-1 (IGF-1) and nerve growth factor (NGF). In the current study, we expand upon on our previous observations by performing an in-depth characterization of the zymosan-modulated neutrophil subsets through scRNAseq and high parameter flow cytometry. Circulating neutrophils, harvested from unmanipulated mice, were analyzed in parallel as a control. We found that each of the unfractionated neutrophil populations is diverse, composed of multiple distinct clusters. Zymosanmodulated 3-day Ly6Glow neutrophils contain a cluster that expresses neuroprotective growth factors in association with markers of alternative activation. Furthermore, the unfractionated neutrophil populations were analyzed by liquid chromatography/ mass spectrometry for proteomic analysis. This new proteomic data identified a wide variety of proteins and pathways that contribute to the alternative activation state of these pro-regenerative 3 day Ly6Glow neutrophils. Collectively, the data generated by the current study constitute another step towards pinpointing the identity and mechanisms of action of pro-regenerative, neuroprotective neutrophil subsets.
2022-06-01 | GSE200445 | GEO
Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained during complex tissue regeneration. Following ERK inhibition, regeneration in Acomys shifted towards a fibrotic repair. Using scRNA-seq, we uncovered that MAPK/ERK signaling acts in a cell type specific manner to direct regenerative healing. Loss- and gain-of-function experiments prompted us to identify FGF and ErbB signaling as upstream ERK regulators of regeneration. By ectopically activating ERK in Mus injuries, a pro- regenerative response was induced, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data provide new insights into why some mammals regenerate better than others and open avenues to redirect fibrotic repair towards regenerative healing.
2023-04-28 | GSE224433 | GEO
Project description:Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained at high levels during complex tissue regeneration. Following ERK inhibition, ear punch regeneration in Acomys shifted towards fibrotic repair. Using scRNA-seq, we identified ERK-responsive cell types. Loss- and gain-of-function experiments prompted us to uncover FGF and ErbB signaling as upstream ERK regulators of regeneration. Strikingly, the ectopic activation of ERK in scar-prone injuries induced a pro-regenerative response, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data detail an important distinction in ERK activity between regenerating and poorly regenerating adult mammals and open avenues to redirect fibrotic repair towards regenerative healing.
2023-04-28 | GSE224879 | GEO
Project description:GSDMD-mediated metabolic crosstalk licenses a pro-regenerative niche for tissue repair
| PRJNA1051656 | ENA