Molecular omics最新文献

{"title":"Untargeted metabolomics analysis reveals spatial metabolic heterogeneity in different intestinal segments of type 1 diabetic mice†","authors":"Kaiyan Gong, Junli Chen, Xiaoli Yin, Mengjun Wu, Hong Zheng and Lingling Jiang","doi":"10.1039/D3MO00163F","DOIUrl":"10.1039/D3MO00163F","url":null,"abstract":"<p >Type 1 diabetes (T1D) has been reported to cause systematic metabolic disorders, but metabolic changes in different intestinal segments of T1D remain unclear. In this study, we analyzed metabolic profiles in the jejunum, ileum, cecum and colon of streptozocin-induced T1D and age-matched control (CON) mice by an LC-MS-based metabolomics method. The results show that segment-specific metabolic disorders occurred in the gut of T1D mice. In the jejunum, we found that T1D mainly led to disordered amino acid metabolism and most amino acids were significantly lower relative to CON mice. Moreover, fatty acid metabolism was disrupted mainly in the ileum, cecum and colon of T1D mice, such as arachidonic acid, alpha-linolenic acid and linoleic acid metabolism. Thus, our study reveals spatial metabolic heterogeneity in the gut of T1D mice and provides a metabolic view on diabetes-associated intestinal diseases.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 2","pages":" 128-137"},"PeriodicalIF":2.9,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135505601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term physical inactivity induces significant changes in biochemical pathways related to metabolism of proteins and glycerophospholipids in mice†","authors":"Bijayashree Sahu, Sunil Pani, Gourabamani Swalsingh, Unmod Senapati, Punyadhara Pani, Benudhara Pati, Subhasmita Rout, Rimjhim Trivedi, Ritu Raj, Suchanda Dey, Amar Jeet, Dinesh Kumar and Naresh C. Bal","doi":"10.1039/D3MO00127J","DOIUrl":"10.1039/D3MO00127J","url":null,"abstract":"<p >Physical inactivity affects multiple organ systems, including the musculoskeletal system, which upsets the delicate balance of several secretory factors leading to metabolic derailment. This reduces contractile recruitment of the skeletal muscle with dampening of its oxidative capacity resulting in impaired intramuscular lipid metabolism and substrate utilization. We hypothesized that this altered phenotype would also have an indispensable effect on circulatory cytokines and the level of metabolic intermediates. In this study, comparison between sedentary (SED) and exercised (EXER) animal models showed that organismal metabolic parameters (body mass, oxygen utilization and glucose tolerance) are altered based on physical activity. Our data suggest that cytokines linked to glycemic excursions (insulin, c-peptide, glucagon) and their passive regulators (leptin, BDNF, active ghrelin, and GIP) exhibit changes in the SED group. Furthermore, some of the proinflammatory cytokines and myokines were upregulated in SED. Interestingly, serum metabolite analysis showed that the levels of glucogenic amino acids (alanine, glycine, tryptophan, proline and valine), nitrogenous amino acids (ornithine, asparagine, and glutamine) and myogenic metabolites (taurine, creatine) were altered due to the level of physical activity. A pyrimidine nucleoside (uridine), lipid metabolite (glycerol) and ketone bodies (acetoacetate and acetate) were found to be altered in SED. A Spearman rank correlation study between SED and CTRL showed that cytokines build a deformed network with metabolites in SED, indicating significant modifications in amino acids, phosphatidylinositol phosphate and glycerophospholipid metabolic pathways. Overall, long-term physical inactivity reorganizes the profile of proinflammatory cytokines, glucose sensing hormones, and protein and glycerophospholipid metabolism, which might be the initial factors of metabolic diseases due to SED.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 64-77"},"PeriodicalIF":2.9,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids","authors":"Lisa Morisseau, Fumiya Tokito, Stéphane Poulain, Valérie Plaisance, Valérie Pawlowski, Soo Hyeon Kim, Cécile Legallais, Rachid Jellali, Yasuyuki Sakai, Amar Abderrahmani and Eric Leclerc","doi":"10.1039/D3MO90033A","DOIUrl":"10.1039/D3MO90033A","url":null,"abstract":"<p >Correction for ‘Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids’ by Lisa Morisseau <em>et al.</em>, <em>Mol. Omics</em>, 2023, https://doi.org/10.1039/d3mo00050h.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 10","pages":" 823-823"},"PeriodicalIF":2.9,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/mo/d3mo90033a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41165889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cronobacter sakazakii infection implicates multifaceted neuro-immune regulatory pathways of Caenorhabditis elegans†","authors":"Lappasi Mohanram VenkataKrishna, Boopathi Balasubramaniam, T. J. Sushmitha, V. Ravichandiran and Krishnaswamy Balamurugan","doi":"10.1039/D3MO00167A","DOIUrl":"10.1039/D3MO00167A","url":null,"abstract":"<p >The neural pathways of <em>Caenorhabditis elegans</em> play a crucial role in regulating host immunity and inflammation during pathogenic infections. To understand the major neuro-immune signaling pathways, this study aimed to identify the key regulatory proteins in the host <em>C. elegans</em> during <em>C. sakazakii</em> infection. We used high-throughput label-free quantitative proteomics and identified 69 differentially expressed proteins. KEGG analysis revealed that <em>C. sakazakii</em> elicited host immune signaling cascades primarily including mTOR signaling, axon regeneration, metabolic pathways (<em>let-363</em> and <em>acox-1.4</em>), calcium signaling <em>(mlck-1)</em>, and longevity regulating pathways (<em>ddl-2</em>), respectively. The abrogation in functional loss of mTOR-associated players deciphered that <em>C. sakazakii</em> infection negatively regulated the lifespan of mutant worms (<em>akt-1</em>, <em>let-363</em> and <em>dlk-1</em>), including physiological aberrations, such as reduced pharyngeal pumping and egg production. Additionally, the candidate pathway proteins were validated by transcriptional profiling of their corresponding genes. Furthermore, immunoblotting showed the downregulation of mTORC2/SGK-1 during the later hours of pathogen exposure. Overall, our findings profoundly provide an understanding of the specificity of proteome imbalance in affecting neuro-immune regulations during <em>C. sakazakii</em> infection.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 48-63"},"PeriodicalIF":2.9,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41206541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of β-like cell subtypes from differentiated human induced pluripotent stem cells in 3D spheroids†","authors":"Lisa Morisseau, Fumiya Tokito, Stéphane Poulain, Valerie Plaisance, Valerie Pawlowski, Soo Hyeon Kim, Cécile Legallais, Rachid Jellali, Yasuyuki Sakai, Amar Abderrahmani and Eric Leclerc","doi":"10.1039/D3MO00050H","DOIUrl":"10.1039/D3MO00050H","url":null,"abstract":"<p >Since the identification of four different pancreatic β-cell subtypes and bi-hormomal cells playing a role in the diabetes pathogenesis, the search for <em>in vitro</em> models that mimics such cells heterogeneity became a key priority in experimental and clinical diabetology. We investigated the potential of human induced pluripotent stem cells to lead to the development of the different β-cells subtypes in honeycomb microwell-based 3D spheroids. The glucose-stimulated insulin secretion confirmed the spheroids functionality. Then, we performed a single cell RNA sequencing of the spheroids. Using a knowledge-based analysis with a stringency on the pancreatic markers, we extracted the β-cells INS+/UCN3+ subtype (11%; β1-like cells), the INS+/ST8SIA1+/CD9− subtype (3%, β3-like cells) and INS+/CD9+/ST8SIA1-subtype (1%; β2-like cells) consistently with literature findings. We did not detect the INS+/ST8SIA1+/CD9+ cells (β4-like cells). Then, we also identified four bi-hormonal cells subpopulations including δ-like cells (INS+/SST+, 6%), γ-like cells (INS+/PPY+, 3%), α-like-cells (INS+/GCG+, 6%) and ε-like-cells (INS+/GHRL+, 2%). Using data-driven clustering, we extracted four progenitors’ subpopulations (with the lower level of INS gene) that included one population highly expressing inhibin genes (INHBA+/INHBB+), one population highly expressing KCNJ3+/TPH1+, one population expressing hepatocyte-like lineage markers (HNF1A+/AFP+), and one population expressing stem-like cell pancreatic progenitor markers (SOX2+/NEUROG3+). Furthermore, among the cycling population we found a large number of REST+ cells and CD9+ cells (CD9+/SPARC+/REST+). Our data confirm that our differentiation leads to large β-cell heterogeneity, which can be used for investigating β-cells plasticity under physiological and pathophysiological conditions.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 10","pages":" 810-822"},"PeriodicalIF":2.9,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer evaluation in dogs using cerumen as a source for volatile biomarker prospection†","authors":"João Marcos G. Barbosa, Engy Shokry, Lurian Caetano David, Naiara Z. Pereira, Adriana R. da Silva, Vilma F. de Oliveira, Maria Clorinda S. Fioravanti, Paulo H. Jorge da Cunha, Anselmo E. de Oliveira and Nelson Roberto Antoniosi Filho","doi":"10.1039/D3MO00147D","DOIUrl":"10.1039/D3MO00147D","url":null,"abstract":"<p >Cancer is one of the deadliest diseases in humans and dogs. Nevertheless, most tumor types spread faster in canines, and early cancer detection methods are necessary to enhance animal survival. Here, cerumen (earwax) was tested as a source of potential biomarkers for cancer evaluation in dogs. Earwax samples from dogs were collected from tumor-bearing and clinically healthy dogs, followed by Headspace/Gas Chromatography-Mass Spectrometry (HS/GC-MS) analyses and multivariate statistical workflow. An evolutionary-based multivariate algorithm selected 18 out of 128 volatile metabolites as a potential cancer biomarker panel in dogs. The candidate biomarkers showed a full discrimination pattern between tumor-bearing dogs and cancer-free canines with high accuracy in the test dataset: an accuracy of 95.0% (75.1–99.9), and sensitivity and specificity of 100.0% and 92.9%, respectively. In summary, this work raises a new perspective on cancer diagnosis in dogs, being carried out painlessly and non-invasive, facilitating sample collection and periodic application in a veterinary routine.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 27-36"},"PeriodicalIF":2.9,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the role of intra-cellular metabolites in the lactic acid production by novel Bacillus amyloliquefaciens using sugarcane molasses as a substratum†","authors":"Balasubramanian Vignesh Kumar, Balakrishnan Muthumari, Murugan Kavitha, John Kennedy John Praveen Kumar and Muthuramalingam Jothi Basu","doi":"10.1039/D3MO00141E","DOIUrl":"10.1039/D3MO00141E","url":null,"abstract":"<p >Lactic acid is a versatile, multi-functional organic monomer in various industries, creating worldwide demand. High titer lactic acid production was achieved by novel <em>Bacillus amyloliquefaciens</em> J2V2AA through sugarcane molasses fermentation up to 178 mg mL<small>⁻¹</small>. A metabolomics approach such as combined GC-MS and LC-MS was applied to elucidate the involvement of key metabolites in lactic acid production. The results revealed the participation of 58 known intra-cellular metabolites at various pathways in lactic acid production. Twenty-eight highly up-regulated and down-regulated metabolites were analyzed, and a schematic diagram of a possible lactic acid production pathway was proposed. The produced lactic acid was analyzed through FTIR, UV-Spectrum, and HPLC analysis.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 19-26"},"PeriodicalIF":2.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of methionine dependence in melanoma cells†","authors":"Sarita Garg, Lauren C. Morehead, Jordan T. Bird, Stefan Graw, Allen Gies, Aaron J. Storey, Alan J. Tackett, Rick D. Edmondson, Samuel G. Mackintosh, Stephanie D. Byrum and Isabelle R. Miousse","doi":"10.1039/D3MO00087G","DOIUrl":"10.1039/D3MO00087G","url":null,"abstract":"<p >Dietary methionine restriction is associated with a reduction in tumor growth in preclinical studies and an increase in lifespan in animal models. The mechanism by which methionine restriction inhibits tumor growth while sparing normal cells is incompletely understood. We do know that normal cells can utilize methionine or homocysteine interchangeably (methionine independence) while most cancer cells are strictly dependent on methionine availability. Here, we compared a typical methionine dependent and a rare methionine independent melanoma cell line. We show that replacing methionine, a methyl donor, with its precursor homocysteine generally induced hypomethylation in gene promoters. This decrease was similar in methionine dependent and methionine independent cells. There was only a low level of pathway enrichment, suggesting that the hypomethylation is generalized rather than gene specific. Whole proteome and transcriptome were also analyzed. This analysis revealed that contrarily to the effect on methylation, the replacement of methionine with homocysteine had a much greater effect on the transcriptome and proteome of methionine dependent cells than methionine independent cells. Interestingly, methionine adenosyltransferase 2A (MAT2A), responsible for the synthesis of <em>S</em>-adenosylmethionine from methionine, was equally strongly upregulated in both cell lines. This suggests that the absence of methionine is equally detected but triggers different outcomes in methionine dependent <em>versus</em> independent cells. Our analysis reveals the importance of cell cycle control, DNA damage repair, translation, nutrient sensing, oxidative stress and immune functions in the cellular response to methionine stress in melanoma.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 37-47"},"PeriodicalIF":2.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing science through data sharing: a new data policy for Molecular Omics","authors":"","doi":"10.1039/D3MO90028B","DOIUrl":"https://doi.org/10.1039/D3MO90028B","url":null,"abstract":"<p >A graphical abstract is available for this content</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 8","pages":" 606-606"},"PeriodicalIF":2.9,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49994739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell proteomics analysis of drug response shows its potential as a drug discovery platform†","authors":"Juerg Straubhaar, Alexandria D’Souza, Zachary Niziolek and Bogdan Budnik","doi":"10.1039/D3MO00124E","DOIUrl":"10.1039/D3MO00124E","url":null,"abstract":"<p >Single-cell analysis has clearly established itself in biology and biomedical fields as an invaluable tool that allows one to comprehensively understand the relationship between cells, including their types, states, transitions, trajectories, and spatial position. Scientific methods such as fluorescence labeling, nanoscale super-resolution microscopy, advances in single cell RNAseq and proteomics technologies, provide more detailed information about biological processes which were not evident with the analysis of bulk material. This new era of single-cell biology provides a better understanding of such complex biological systems as cancer, inflammation, immunity mechanism and aging processes, and opens the door into the field of drug response heterogeneity. The latest discoveries of cellular heterogeneity gives us a unique understanding of complex biological processes, such as disease mechanism, and will lead to new strategies for better and personalized treatment strategies. Recently, single-cell proteomics techniques that allow quantification of thousands of proteins from single mammalian cells have been introduced. Here we present an improved single-cell mass spectrometry-based proteomics platform called SCREEN (<strong>S</strong>ingle <strong>C</strong>ell p<strong>R</strong>ot<strong>E</strong>om<strong>E</strong> a<strong>N</strong>alysis) for deep and high-throughput single-cell proteome coverage with high efficiency, less turnaround time and with an improved ability for protein quantitation across more cells than previously achieved. We applied this new platform to analyze the single-cell proteomic landscape under different drug treatment over time to uncover heterogeneity in cancer cell response, which for the first time, to our knowledge, has been achieved by mass spectrometry based analytical methods. We discuss challenges in single-cell proteomics, future improvements and general trends with the goal to encourage forthcoming technical developments.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 1","pages":" 6-18"},"PeriodicalIF":2.9,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}