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Transcription Factor Activity Regulating Macrophage Heterogeneity during Skin Wound Healing

ABSTRACT: Transcription Factor Activity Regulating Macrophage Heterogeneity during Skin Wound Healing

PROVIDER: PRJNA1053360 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27228370_1.fastq.gz	Fastqsanger.gz
	SRR27228370_2.fastq.gz	Fastqsanger.gz
	SRR27228371_1.fastq.gz	Fastqsanger.gz
	SRR27228371_2.fastq.gz	Fastqsanger.gz
	SRR27228372_1.fastq.gz	Fastqsanger.gz

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Monocyte/macrophage heterogeneity during skin wound healing in mice

Project description:Monocyte/macrophage heterogeneity during skin wound healing in mice

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Transcription Factor Activity Regulating Macrophage Heterogeneity during Skin Wound Healing

Project description:We aimed to study chromatin accessibility for TF binding sites for inferring TF activity in monocytes and macrophages during skin wound healing. Monocytes and macrophages isolated from skin wounds on male C57BL6/J mice on day 3 and 6 post-injury, subjected to enzymatic digestion to obtain single cells and pooled from two mice per time point. Nuclei were processed using the 10x Chromium platform. Libraries sequenced on NovaSeq 6000 with paired-end reads. Fastq files were generated and demultiplexed into single cells using Cell Ranger software.

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Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.

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