Macrophage histone lactylation during ischemia induced-muscle regeneration [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA1068612 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27717952_1.fastq.gz | Fastqsanger.gz | |||
| SRR27717952_2.fastq.gz | Fastqsanger.gz | |||
| SRR27717953_1.fastq.gz | Fastqsanger.gz | |||
| SRR27717953_2.fastq.gz | Fastqsanger.gz | |||
| SRR27717954_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Macrophage histone lactylation during ischemia induced-muscle regeneration
| PRJNA1068601 | ENA
Project description:Macrophage histone lactylation during ischemia induced-muscle regeneration [CUT&Tag]
| PRJNA1068610 | ENA
Project description:After injury, muscles require fully functional macrophages to recover completely. During muscle regeneration, macrophages transition from a pro-inflammatory to a pro-restorative phenotype ensures the proper regeneration. Lactate is a crucial molecule for muscle-residing macrophage polarisation. Histone lactylation, a direct derivative of lactate, has been implicated in macrophage polarisation in vitro . In this work, we show for the first time that macrophages recruited to the muscle after ischemic injury modify their histone lactylome between 2 and 4 days post injury. Absolute histone lactylation levels increase significantly. Although subtly, also the genomic enrichment of H3K18la changes from 2 to 4 days post injury and this correlates with gene expression changes. Interestingly, we find that H3K18la genomic enrichment changes from day 2 to day 4 post injury are predictive for gene expression changes later in time, from day 4 to day 7, rather than being a reflection of past gene expression changes from day 1 to day 2. Our results suggest that histone lactylation dynamics are functionally important for the resolving action of macrophages during muscle regeneration.
2024-04-08 | GSE254129 | GEO
Project description:After injury, muscles require fully functional macrophages to recover completely. During muscle regeneration, macrophages transition from a pro-inflammatory to a pro-restorative phenotype ensures the proper regeneration. Lactate is a crucial molecule for muscle-residing macrophage polarisation. Histone lactylation, a direct derivative of lactate, has been implicated in macrophage polarisation in vitro . In this work, we show for the first time that macrophages recruited to the muscle after ischemic injury modify their histone lactylome between 2 and 4 days post injury. Absolute histone lactylation levels increase significantly. Although subtly, also the genomic enrichment of H3K18la changes from 2 to 4 days post injury and this correlates with gene expression changes. Interestingly, we find that H3K18la genomic enrichment changes from day 2 to day 4 post injury are predictive for gene expression changes later in time, from day 4 to day 7, rather than being a reflection of past gene expression changes from day 1 to day 2. Our results suggest that histone lactylation dynamics are functionally important for the resolving action of macrophages during muscle regeneration.
2024-04-08 | GSE254128 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-08 | GSE254131 | GEO
Project description:Immune responses and neuroinflammation occurring after acute ischemic stroke (AIS) are closely related to brain injury. Histone lactylation is a metabolic stress-related histone modification that participates in the pathogenesis of various diseases. However, the role of histone regulation in cerebral ischemic stroke remains unknown. In this study, a transient middle cerebral artery occlusion (tMCAO/R) model and an oxygen–glucose deprivation and reoxygenation (OGD/R) model were used to simulate in vivo/in vitro ischemia–reperfusion injury. The underlying mechanism of microglial histone lactylation was investigated using microglia-specific SMEK1-overexpressing mice and BV2 cells. The results showed that lactate overload resulted in elevated histone lactylation after AIS. Decreased SMEK1 expression in microglia after ischemic stroke was associated with increased lactate levels and subsequent neuroinflammation. Microglia-specific SMEK1 deficiency in microglia after ischemia can promote lactate production by inhibiting the pyruvate dehydrogenase kinase 3-pyruvate dehydrogenase (PDK3-PDH) pathway. Specifically, H3 lysine 9 lactylation (H3K9la) activated Ldha and Hif-1α transcription in microglia and promoted glycolysis. SMEK1-overexpressing mice exhibited better neurologic recovery after ischemic stroke than control mice. Mechanistically, we provided new evidence that microglial histone lactylation promoted glycolysis in ischemia‒reperfusion injury and elucidated the potential role of SMEK1 as an upstream regulatory molecule in histone lactylation after cerebral ischemia. According to our results, microglial SMEK1 may be potential therapeutic targets for AIS.
2025-01-02 | GSE283233 | GEO
Project description:ObjectivesWe have previously shown that lactate is an essential metabolite for macrophage polarisation during ischemia-induced muscle regeneration. Recent in vitro work has implicated histone lactylation, a direct derivative of lactate, in macrophage polarisation. Here, we explore the in vivo relevance of histone lactylation for macrophage polarisation after muscle injury.MethodsTo evaluate macrophage dynamics during muscle regeneration, we subjected mice to ischemia-induced muscle damage by ligating the femoral artery. Muscle samples were harvested at 1, 2, 4, and 7 days post injury (dpi). CD45+CD11b+F4/80+CD64+ macrophages were isolated and processed for RNA sequencing, Western Blotting, and CUT&Tag-sequencing to investigate gene expression, histone lactylation levels, and histone lactylation genomic localisation and enrichment, respectively.ResultsWe show that, over time, macrophages in the injured muscle undergo extensive gene expression changes, which are similar in nature and in timing to those seen after other types of muscle-injuries. We find that the macrophage histone lactylome is modified between 2 and 4 dpi, which is a crucial window for macrophage polarisation. Absolute histone lactylation levels increase, and, although subtly, the genomic enrichment of H3K18la changes. Overall, we find that histone lactylation is important at both promoter and enhancer elements. Lastly, H3K18la genomic profile changes from 2 to 4 dpi were predictive for gene expression changes later in time, rather than being a reflection of prior gene expression changes.ConclusionsOur results suggest that histone lactylation dynamics are functionally important for the function of macrophages during muscle regeneration.
| S-EPMC11002880 | biostudies-literature
Project description:Cancer-augmented lactogenesis has been described by the Warburg effect, and is associated with several major hallmarks of neoplasia. However, the non-metabolic functions of elevated lactate in physiology and disease remain unknown. Here we report histone lysine lactylation as a new type of epigenetic mechanism and as a functional destination for lactate. Histone lactylation is induced under glycolytic conditions such as hypoxia and M1 macrophage polarization. In the late phase of M1 macrophage polarization, increases in histone lactylation but not acetylation mark M2-like genes for activation. Our findings suggest a feedback mechanism of the innate immune system to switch from proinflammation to resolution through histone Kla-associated gene expression. This mechanism is implemented by the coopted function of lactate and histone lactylation in metabolism and epigenetics. Together, our study opens a new avenue for understanding function of lactate and glycolysis underlined diverse pathophysiological conditions.
2019-08-06 | GSE115354 | GEO
Project description:Macrophage activation is a hallmark of atherosclerosis, accompanied by a switch in core metabolism from oxidative phosphorylation to glycolysis. The crosstalk between metabolic rewiring and epigenetic modifications in macrophages is worthy of further investigation. Here, we found that lactate efflux-associated monocarboxylate transporter 4 (MCT4)-mediated histone lactylation is closely related to atherosclerosis. Histone H3 lysine 18 lactylation dependent on MCT4 deficiency activated the transcription of anti-inflammatory genes and tricarboxylic acid cycle genes, resulting in the initiation of local repair and homeostasis. Strikingly, histone lactylation is characteristically involved in the stage-specific local repair process during M1 to M2 transformation, whereas histone methylation and acetylation are not. Gene manipulation and protein hydrolysis-targeted chimerism (PROTAC) technology were used to confirm that MCT4 deficiency favors ameliorating atherosclerosis. Therefore, our study shows that macrophage MCT4 deficiency, which links metabolic rewiring and epigenetic remodeling, plays a key role in training macrophages to become repair and homeostasis phenotypes.
2024-04-08 | GSE262808 | GEO
Project description:CD34+ cells improve the perfusion and function of ischemic limbs in humans and mice. However, there is no direct evidence of the differentiation potential and functional role of these cells in the ischemic muscle microenvironment. Here, we combined the single-cell RNA sequencing and genetic lineage tracing technology and then provided exact single-cell atlases of normal and ischemic limb tissues in human and mouse, consequently found that bone marrow-derived macrophages with antigen-presenting function migrated to the ischemic site, while resident macrophages underwent apoptosis. The macrophage oncostatin M (OSM) regulatory pathway was specifically turned on by ischemia. Simultaneously, bone marrow CD34+-derived pro-regenerative fibroblasts were recruited to the ischemia niche, where they received macrophage-released OSM, and promoted angiopoietin-like protein (ANGPTL)-associated angiogenesis. These findings provided novel mechanisms on the cellular events and cell–cell communications during tissue ischemia and regeneration, and provided new evidence that CD34+ cells serve as fibroblast progenitors promoting tissue regeneration.
2023-09-05 | GSE215922 | GEO