Proteomics and Lactylome of osteoblast differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Pengbin Yin
PROVIDER: PXD069298 | iProX | Thu Oct 09 00:00:00 BST 2025
REPOSITORIES: iProX
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Project description:Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM), which participates in gene expression and various metabolic processes. Nannochloropsis, a significant oleaginous microalgae of economic significance, demonstrates a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted ChIP-seq and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2,057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions, comprising 853 upregulated genes and 1,204 downregulated genes. Moreover, a total of 5,375 differential Kla peaks were identified, including 5,331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (<= 1 kb) (71.07%), 5’UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and β-oxidation pathways. This research reveals the regulatory functions of lactylation in lipid metabolism and gene expression in Nannochloropsis, offering a new perspective for the investigation of lipid biosynthesis.
2024-06-26 | GSE261019 | GEO
Project description:Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM), which participates in gene expression and various metabolic processes. Nannochloropsis, a significant oleaginous microalgae of economic significance, demonstrates a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted ChIP-seq and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2,057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions, comprising 853 upregulated genes and 1,204 downregulated genes. Moreover, a total of 5,375 differential Kla peaks were identified, including 5,331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (<= 1 kb) (71.07%), 5’UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and β-oxidation pathways. This research reveals the regulatory functions of lactylation in lipid metabolism and gene expression in Nannochloropsis, offering a new perspective for the investigation of lipid biosynthesis.
2024-06-26 | GSE260894 | GEO
Project description:Myopia has become the major cause of visual impairment worldwide. Although the pathogenesis of myopia remains controversial, proteomics studies suggest that dysregulation of retinal metabolism is potentially involved in the pathology of myopia. Lysine lactylation of proteins plays a key role in regulating cellular metabolism, but little is known about its role in the form-deprived myopic retina. In this study, we performed lactylation proteomic analysis of the retinas of form-deprived myopic guinea pigs and found downregulated levels of lactylation of metabolism-critical enzymes in the retina. As the first report on retinal lactylation in myopic eyes, this study provides a reliable basis for further studies on retinal lactylation in myopic eyes.
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Project description:Lysine lactylation as a type of posttranslational modifications (PTMs) is recently associated with chromatin remodeling and gene transcription, but lysine lactylation of histone and non-histone proteins has not yet been studied in Nannochloropsis oceanica. To examine the prevalence and function of lactylation in N. oceanica, protein lactylation modification profiles were tracked after nitrogen deprivation for three days using 4D label-free proteome method. Under nitrogen deprivation (ND) and nitrogen repletion (NR) cultivation conditions, we mapped lactylome of proliferating microalgal cells.
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Project description:Acute myeloid leukemia (AML) is characterized by developmental arrest which is thought to arise from transcriptional dysregulation of myeloid development programs. Here, we have analyzed the transcriptome of AML blasts in comparison with normal human CD34+ cells using the HTA 2.0 gene chip. We have compared 18 minimally differentiated AML blasts with cord blood derived normal human CD34+ cells - this study is performed as a parallel analysis to compliment the nuclear proteomic studies.
2019-10-02 | E-MTAB-3873 | biostudies-arrayexpress
Project description:Lysine lactylation (Kla) is a newly discovered posttranslational modification showing the addition of an L-lactate-derived lactyl group to the lysine residue. Histone lactylation has been found to regulate the downstream genes expression involved in the process of infection clearance, homeostasis retore, and tumorigenesis. Like other metabolite mediated PTMs, which the cellular levels of these metabolites affect the stoichiometry of the corresponding PTMs, the level of Kla also responds to the intracellular lactate concentration in a dose-dependent fashion associated with glycolysis metabolism. It has long been noted that manipulation of glycolysis metabolism could affect the tendon cell function, tendon homeostasis, and healing process of tendon.Nonetheless, the lactylation sites and regulations in tendinopathy remain unexplored.
2023-05-10 | PXD033146 | Pride
Project description:In this study, we evaluated the utility of proteomics to identify plasma proteins in healthy participants from a phase I clinical trial with IFNβ-1a and pegIFNβ-1a biologics to identify potential pharmacodynamic (PD) biomarkers. Using a linear mixed-effects model with repeated measurement for product-time interaction, we found that 248 and 528 analytes detected by the SOMAscan® assay were differentially expressed (p-value < 6.86E-06) between therapeutic doses of IFNβ-1a or pegIFNβ-1a, and placebo, respectively. We further prioritized signals based on peak change, area under the effect curve over the study duration, and overlap in signals from the two products. Analysis of prioritized datasets indicated activation of IFNB1 signaling and an IFNB signaling node with IL-6 as upstream regulators of the plasma protein patterns from both products. Increased TNF, IL-1B, IFNG, and IFNA signaling also occurred early in response to each product suggesting a direct link between each product and these upstream regulators. In summary, we identified longitudinal global PD changes in a large array of new and previously reported circulating proteins in healthy participants treated with IFNβ-1a and pegIFNβ-1a that may help identify novel single proteomic PD biomarkers and/or composite PD biomarker signatures as well as provide insight into the mechanism of action of these products. Independent replication is needed to confirm present proteomic results and to support further investigation of the identified candidate PD biomarkers for biosimilar product development.
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Project description:To explore the effects of moderate intensity exercise on protein of lactylation in mouse muscle tissue metabolism. The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, lactylation-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well.
2024-08-21 | GSE270280 | GEO
Project description:Dysregulation of Th17 differentiation was implicated in multiple inflammatory and autoimmune diseases including autoimmune uveitis. In the current study, we have provided evidence indicating that lactate-derived lactylation plays important roles in regulating Th17 differentiation. The lactylation level of CD4+ T cells was upregulated in EAU mice and inhibiting lactylation resulted in impaired EAU progression. We characterized the global lactylome of CD4+ T cells of normal and EAU mice. We found that the differentially lactylated proteins were enriched in pathways related to immune responses including leukocyte differentiation. Importantly, our results show that the lactylation level of Ikzf1 (K164) functions in regulating Th17 differentiation by differentially modulating gene expression patterns which are related to CD4+ T cell differentiation by CUT& Tag analysis. In view of the above mentioned well-documented evidence, Ikzf1 lactylation might represent an important regulator for Th17 differentiation in autoimmune uveitis.
2023-08-28 | GSE226678 | GEO
Project description:Dysregulation of CD4+ T cell differentiation is linked to autoimmune diseases. Metabolic reprogramming from oxidative phosphorylation to glycolysis and accumulation of lactate are involved in this process. However, the underlying mechanisms remain unclear. Our study showed that lactate-derived lactylation regulated CD4+ T cell differentiation. Lactylation levels in CD4+ T cells increased with the progression of experimental autoimmune uveitis (EAU). Inhibition of lactylation suppressed TH17 differentiation and attenuated EAU inflammation. The global lactylome revealed the landscape of lactylated sites and proteins in the CD4+ T cells of normal and EAU mice. Specifically, hyperlactylation of Ikzf1 at Lys164 promoted TH17 differentiation by directly modulating the expression of TH17-related genes, including Runx1, Tlr4, interleukin-2 (IL-2), and IL-4. Delactylation of Ikzf1 at Lys164 impaired TH17 differentiation. These findings exemplify how glycolysis regulates the site specificity of protein lactylation to promote TH17 differentiation and implicate Ikzf1 lactylation as a potential therapeutic target for autoimmune diseases.
| S-EPMC10584346 | biostudies-literature