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Premature ovarian insufficiency (POI) is a major cause of infertility and endocrine dysfunction, in which chronic inflammation plays a critical role. The homeostasis of tissue-resident macrophages and monocyte-differentiated macrophages from peripheral blood serves as a key mechanism of inflammation across organs, yet their phenotypic plasticity in ovarian pathologies, including POI, remains poorly understood. Here, we identify that SIRT5 deficiency decreases macrophage count by attenuating monocyte-macrophage differentiation. SIRT5 deficiency markedly attenuated follicular depletion and granulosa cell apoptosis, coinciding with reduced M1 macrophage infiltration and cytokine expression in the POI model. Mechanistically, we uncovered RAC2 as a novel succinylation substrate of SIRT5. SIRT5 deficiency elevated RAC2 succinylation, promoting its proteasomal degradation and thereby impairing CSF1R-driven macrophage differentiation and M1 polarization. Pharmacological inhibition of SIRT5 recapitulated these protective effects, preserving follicular integrity and suppressing macrophage-mediated inflammation. Our findings identify the SIRT5-RAC2 axis as a key regulator of ovarian immune homeostasis and establish SIRT5 as a proof-of-concept therapeutic target for POI.
Pubmed ID: 41498691
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Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware tool to automate quality and adapter trimming as well as quality control, with some added functionality to remove biased methylation positions for RRBS sequence files for directional, non-directional or paired-end sequencing. Wrapper around Cutadapt and FastQC to consistently apply adapter and quality trimming to FastQ files, with extra functionality for Reduced Representation Bisulfite Sequencing data.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsSoftware R package for statistical analysis and visualization of functional profiles for genes and gene clusters.
View all literature mentionsPortal used to find and download any of data sets published on CELLxGENE. Allows to download and visually explore data to understand functionality of human tissues at cellular level. Optimized for finding, exploring, and reusing single cell data. Collections Page lists collections hosted on CELLxGENE Discover and metadata that define tissue, assay, disease, organism, and cell count for each collection. Once you find published dataset of interest on CELLxGENE Discover, you can click on the explore button below the dataset description to explore the cells of that dataset using the CELLxGENE Explorer.
View all literature mentionsProvides open access to suite of resources, with the aim to translate big data into big discoveries. Offers range of resources for biological big data deposition, integration, and translation.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line KGN is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
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