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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15 [scRNA-seq]

ABSTRACT: A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15 [scRNA-seq]

PROVIDER: PRJNA678349 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13057910_1.fastq.gz	Fastqsanger.gz
	SRR13057910_2.fastq.gz	Fastqsanger.gz

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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

Project description:A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

Project description:A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

Project description:Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Proinflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed Regeneration-Promoting Program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-beta superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARg. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (Growth Factor-Expressing Macrophages, GFEM).

2021-11-16 | GSE182455 | GEO

A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15 [scRNA-seq]

Project description:Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Proinflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed Regeneration-Promoting Program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-beta superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARg. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is co-expressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (Growth Factor-Expressing Macrophages, GFEM).

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A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15.

Project description:Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-β superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).

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A Growth Factor-Expressing Macrophage subpopulation orchestrates regenerative inflammation via GDF-15

Project description:This SuperSeries is composed of the SubSeries listed below.

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Neuronal GDF-15 delivery alters peripheral CD4+ T cell phenotype

Project description:In this study we investigated the immunomodulatory properties of GDF-15 in the context of neuroinflammation. We exploited neuronal gene therapy to overexpress GDF-15 within the central nervous system, which protected mice from developing any clinical signs of neuroinflammation in the experimental autoimmune encephalitis (EAE) model. We discovered that GDF-15 delivery modulated the peripheral T cell response and prevented immune cells from transmigrating into the central nervous system.

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Distinct Fibroblast Progenitor Subpopulation Expedites Regenerative Mucosal Healing by Immunomodulation

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