دورية أكاديمية
Key signaling networks are dysregulated in patients with the adipose tissue disorder, lipedema.
| العنوان: | Key signaling networks are dysregulated in patients with the adipose tissue disorder, lipedema. |
|---|---|
| المؤلفون: | Ishaq M; Lymphatic, Adipose and Regenerative Medicine Laboratory, O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia. ishaqmusarat@gmail.com.; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia. ishaqmusarat@gmail.com., Bandara N; Lymphatic, Adipose and Regenerative Medicine Laboratory, O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia., Morgan S; Lymphatic, Adipose and Regenerative Medicine Laboratory, O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia., Nowell C; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia., Mehdi AM; Diamantia Institute, Faculty of Medicine, The University of Queensland, St Lucia, QLD, 4067, Australia., Lyu R; Bioinformatics and Cellular Genomics, St. Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia., McCarthy D; Bioinformatics and Cellular Genomics, St. Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia., Anderson D; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia., Creek DJ; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia., Achen MG; Lymphatic, Adipose and Regenerative Medicine Laboratory, O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia.; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia., Shayan R; Lymphatic, Adipose and Regenerative Medicine Laboratory, O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia.; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia., Karnezis T; Lymphatic, Adipose and Regenerative Medicine Laboratory, O'Brien Institute Department, St Vincent's Institute of Medical Research, Fitzroy, VIC, 3065, Australia. tkarnezis@svi.edu.au.; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia. tkarnezis@svi.edu.au. |
| المصدر: | International journal of obesity (2005) [Int J Obes (Lond)] 2022 Mar; Vol. 46 (3), pp. 502-514. Date of Electronic Publication: 2021 Nov 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101256108 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5497 (Electronic) Linking ISSN: 03070565 NLM ISO Abbreviation: Int J Obes (Lond) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Pub. Group, c2005- |
| مواضيع طبية MeSH: | Lipedema*/genetics, Adipocytes/metabolism ; Adipogenesis/genetics ; Adipose Tissue/metabolism ; Cell Differentiation/physiology ; Humans ; Lipids |
| مستخلص: | Objectives: Lipedema, a poorly understood chronic disease of adipose hyper-deposition, is often mistaken for obesity and causes significant impairment to mobility and quality-of-life. To identify molecular mechanisms underpinning lipedema, we employed comprehensive omics-based comparative analyses of whole tissue, adipocyte precursors (adipose-derived stem cells (ADSCs)), and adipocytes from patients with or without lipedema. Methods: We compared whole-tissues, ADSCs, and adipocytes from body mass index-matched lipedema (n = 14) and unaffected (n = 10) patients using comprehensive global lipidomic and metabolomic analyses, transcriptional profiling, and functional assays. Results: Transcriptional profiling revealed >4400 significant differences in lipedema tissue, with altered levels of mRNAs involved in critical signaling and cell function-regulating pathways (e.g., lipid metabolism and cell-cycle/proliferation). Functional assays showed accelerated ADSC proliferation and differentiation in lipedema. Profiling lipedema adipocytes revealed >900 changes in lipid composition and >600 differentially altered metabolites. Transcriptional profiling of lipedema ADSCs and non-lipedema ADSCs revealed significant differential expression of >3400 genes including some involved in extracellular matrix and cell-cycle/proliferation signaling pathways. One upregulated gene in lipedema ADSCs, Bub1, encodes a cell-cycle regulator, central to the kinetochore complex, which regulates several histone proteins involved in cell proliferation. Downstream signaling analysis of lipedema ADSCs demonstrated enhanced activation of histone H2A, a key cell proliferation driver and Bub1 target. Critically, hyperproliferation exhibited by lipedema ADSCs was inhibited by the small molecule Bub1 inhibitor 2OH-BNPP1 and by CRISPR/Cas9-mediated Bub1 gene depletion. Conclusion: We found significant differences in gene expression, and lipid and metabolite profiles, in tissue, ADSCs, and adipocytes from lipedema patients compared to non-affected controls. Functional assays demonstrated that dysregulated Bub1 signaling drives increased proliferation of lipedema ADSCs, suggesting a potential mechanism for enhanced adipogenesis in lipedema. Importantly, our characterization of signaling networks driving lipedema identifies potential molecular targets, including Bub1, for novel lipedema therapeutics. (© 2021. The Author(s).) |
| References: | Child AH, Gordon KD, Sharpe P, Brice G, Ostergaard P, Jeffery S, et al. Lipedema: an inherited condition. Am J Med Genet A. 2010;152A:970–6. (PMID: 2035861110.1002/ajmg.a.33313) Buck DW II, Herbst KL. Lipedema: a relatively common disease with extremely common misconceptions. Plast Reconstr Surg Glob Open. 2016;4:e1043. (PMID: 27757353505501910.1097/GOX.0000000000001043) Paolacci S, Precone V, Acquaviva F, Chiurazzi P, Fulcheri E, Pinelli M, et al. Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. Eur Rev Med Pharmacol Sci. 2019;23:5581–94. (PMID: 31298310) Tchernof A, Despres JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93:359–404. (PMID: 2330391310.1152/physrev.00033.2011) Porter SA, Massaro JM, Hoffmann U, Vasan RS, O’Donnel CJ, Fox CS. Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care. 2009;32:1068–75. (PMID: 19244087268103410.2337/dc08-2280) Canning C, Bartholomew JR. Lipedema. Vasc Med. 2018;23:88–90. (PMID: 2914357710.1177/1358863X17739698) Caruana M. Lipedema: a commonly misdiagnosed fat disorder. Plast Surg Nurs. 2018;38:149–52. (PMID: 3050781310.1097/PSN.0000000000000245) Torre YS, Wadeea R, Rosas V, Herbst KL. Lipedema: friend and foe. Horm Mol Biol Clin Investig. 2018;33. Al-Ghadban S, Diaz ZT, Singer HJ, Mert KB, Bunnell BA. Increase in leptin and PPAR-gamma gene expression in lipedema adipocytes differentiated in vitro from adipose-derived stem cells. Cells. 2020;9:430. Al-Ghadban S, Pursell IA, Diaz ZT, Herbst KL, Bunnell BA. 3D spheroids derived from human lipedema ASCs demonstrated similar adipogenic differentiation potential and ECM remodeling to non-lipedema ASCs in vitro. Int J Mol Sci. 2020;21:8350. Pereira de Godoy LM, Pereira de Godoy HJ, Pereira de Godoy Capeletto P, Guerreiro Godoy MF, Pereira de Godoy JM. Lipedema and the evolution to lymphedema with the progression of obesity. Cureus. 2020;12:e11854. (PMID: 332826087714724) Priglinger E, Strohmeier K, Weigl M, Lindner C, Auer D, Gimona M, et al. SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema. Sci Rep. 2020;10:7211. (PMID: 32350368719063310.1038/s41598-020-64215-w) Ryden M, Andersson DP, Bergstrom IB, Arner P. Adipose tissue and metabolic alterations: regional differences in fat cell size and number matter, but differently: a cross-sectional study. J Clin Endocrinol Metab. 2014;99:E1870–6. (PMID: 2493753610.1210/jc.2014-1526) Hoffstedt J, Arner E, Wahrenberg H, Andersson DP, Qvisth V, Lofgren P, et al. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia. 2010;53:2496–503. (PMID: 2083046610.1007/s00125-010-1889-3) Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121:2094–101. (PMID: 21633177310476110.1172/JCI45887) Kim SM, Lun M, Wang M, Senyo SE, Guillermier C, Patwari P, et al. Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance. Cell Metab. 2014;20:1049–58. (PMID: 25456741471537510.1016/j.cmet.2014.10.010) Al-Ghadban S, Cromer W, Allen M, Ussery C, Badowski M, Harris D, et al. Dilated blood and lymphatic microvessels, angiogenesis, increased macrophages, and adipocyte hypertrophy in lipedema thigh skin and fat tissue. J Obes. 2019;2019:8747461. (PMID: 30949365642541110.1155/2019/8747461) Mattar P, Bieback K. Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells. Front Immunol. 2015;6:560. (PMID: 26579133463065910.3389/fimmu.2015.00560) Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15:641–8. (PMID: 23570660397943510.1016/j.jcyt.2013.02.006) Rodriguez AM, Elabd C, Delteil F, Astier J, Vernochet C, Saint-Marc P, et al. Adipocyte differentiation of multipotent cells established from human adipose tissue. Biochem Biophys Res Commun. 2004;315:255–63. (PMID: 1476620210.1016/j.bbrc.2004.01.053) Dicker A, Le Blanc K, Astrom G, van Harmelen V, Gotherstrom C, Blomqvist L, et al. Functional studies of mesenchymal stem cells derived from adult human adipose tissue. Exp Cell Res. 2005;308:283–90. (PMID: 1592536410.1016/j.yexcr.2005.04.029) Nepali S, Park M, Lew H, Kim O. Comparative analysis of human adipose-derived mesenchymal stem cells from orbital and abdominal fat. Stem Cells Int. 2018;2018:3932615. (PMID: 30210548612025810.1155/2018/3932615) Perrini S, Laviola L, Cignarelli A, Melchiorre M, De Stefano F, Caccioppoli C, et al. Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells. Diabetologia. 2008;51:155–64. (PMID: 1796036010.1007/s00125-007-0841-7) Fei W, Du X, Yang H. Seipin, adipogenesis and lipid droplets. Trends Endocrinol Metab. 2011;22:204–10. (PMID: 2149751310.1016/j.tem.2011.02.004) Shukla L, Yuan Y, Shayan R, Greening DW, Karnezis T. Fat therapeutics: the clinical capacity of adipose-derived stem cells and exosomes for human disease and tissue regeneration. Front Pharmacol. 2020;11:158. (PMID: 32194404706267910.3389/fphar.2020.00158) De Leon H, Boue S, Szostak J, Peitsch MC, Hoeng J. Systems biology research into cardiovascular disease: contributions of lipidomics-based approaches to biomarker discovery. Curr Drug Discov Technol. 2015;12:129–54. (PMID: 2613585510.2174/1570163812666150702123319) Lappas M, Mundra PA, Wong G, Huynh K, Jinks D, Georgiou HM, et al. The prediction of type 2 diabetes in women with previous gestational diabetes mellitus using lipidomics. Diabetologia. 2015;58:1436–42. (PMID: 2589372910.1007/s00125-015-3587-7) Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab. 2012;97:2482–8. (PMID: 22508708338740810.1210/jc.2011-3475) Berger JP. Role of PPARgamma, transcriptional cofactors, and adiponectin in the regulation of nutrient metabolism, adipogenesis and insulin action: view from the chair. Int J Obes (Lond). 2005;29(Suppl 1):S3–4. (PMID: 10.1038/sj.ijo.0802904) Lavrov AV, Smirnichina SA. [Nuclear heterogeneity and proliferative capacity of human adipose derived MSC-like cells]. Tsitologiia. 2010;52:616–20. (PMID: 20968094) Barr AR, Cooper S, Heldt FS, Butera F, Stoy H, Mansfeld J, et al. DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression. Nat Commun. 2017;8:14728. (PMID: 28317845536438910.1038/ncomms14728) Grabsch H, Takeno S, Parsons WJ, Pomjanski N, Boecking A, Gabbert HE, et al. Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer-association with tumour cell proliferation. J Pathol. 2003;200:16–22. (PMID: 1269283610.1002/path.1324) Zhu LJ, Pan Y, Chen XY, Hou PF. BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation. Oncol Lett. 2020;19:3506–12. (PMID: 322696247114935) Asghar A, Lajeunesse A, Dulla K, Combes G, Thebault P, Nigg EA, et al. Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation. Nat Commun. 2015;6:8364. (PMID: 2639932510.1038/ncomms9364) Moustakas A. The mitotic checkpoint protein kinase BUB1 is an engine in the TGF-beta signaling apparatus. Sci Signal. 2015;8:fs1. (PMID: 2558718910.1126/scisignal.aaa4636) Paganelli L, Caillaud MC, Quentin M, Damiani I, Govetto B, Lecomte P, et al. Three BUB1 and BUBR1/MAD3-related spindle assembly checkpoint proteins are required for accurate mitosis in Arabidopsis. New Phytol. 2015;205:202–15. (PMID: 2526277710.1111/nph.13073) Wang Z, Katsaros D, Shen Y, Fu Y, Canuto EM, Benedetto C, et al. Biological and clinical significance of MAD2L1 and BUB1, genes frequently appearing in expression signatures for breast cancer prognosis. PLoS One. 2015;10:e0136246. (PMID: 26287798454611710.1371/journal.pone.0136246) Myrie KA, Percy MJ, Azim JN, Neeley CK, Petty EM. Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines. Cancer Lett. 2000;152:193–9. (PMID: 1077341210.1016/S0304-3835(00)00340-2) Ouyang B, Knauf JA, Ain K, Nacev B, Fagin JA. Mechanisms of aneuploidy in thyroid cancer cell lines and tissues: evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1. Clin Endocrinol (Oxf). 2002;56:341–50. (PMID: 10.1046/j.1365-2265.2002.01475.x) Grabsch HI, Askham JM, Morrison EE, Pomjanski N, Lickvers K, Parsons WJ, et al. Expression of BUB1 protein in gastric cancer correlates with the histological subtype, but not with DNA ploidy or microsatellite instability. J Pathol. 2004;202:208–14. (PMID: 1474350310.1002/path.1499) Grigorova M, Staines JM, Ozdag H, Caldas C, Edwards PA. Possible causes of chromosome instability: comparison of chromosomal abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1. Cytogenet Genome Res. 2004;104:333–40. (PMID: 1516206110.1159/000077512) Breit C, Bange T, Petrovic A, Weir JR, Muller F, Vogt D, et al. Role of intrinsic and extrinsic factors in the regulation of the mitotic checkpoint kinase Bub1. PLoS One. 2015;10:e0144673. (PMID: 26658523467552410.1371/journal.pone.0144673) Han JY, Han YK, Park GY, Kim SD, Lee CG. Bub1 is required for maintaining cancer stem cells in breast cancer cell lines. Sci Rep. 2015;5:15993. (PMID: 26522589462916410.1038/srep15993) Ricke RM, Jeganathan KB, van Deursen JM. Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation. J Cell Biol. 2011;193:1049–64. (PMID: 21646403311579910.1083/jcb.201012035) Tang Z, Sun Y, Harley SE, Zou H, Yu H. Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis. Proc Natl Acad Sci U S A. 2004;101:18012–7. (PMID: 1560415253981710.1073/pnas.0408600102) Nyati S, Schinske-Sebolt K, Pitchiaya S, Chekhovskiy K, Chator A, Chaudhry N, et al. The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-beta signaling. Sci Signal. 2015;8:ra1. (PMID: 25564677444054410.1126/scisignal.2005379) Brimacombe CA, Burke JE, Parsa JY, Catania S, O’Meara TR, Witchley JN, et al. A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in Candida albicans. PLoS Biol. 2019;17:e3000331. (PMID: 31226107661369510.1371/journal.pbio.3000331) Kobayashi Y, Kawashima SA. Bub1 kinase- and H2A phosphorylation-independent regulation of Shugoshin proteins under glucose-restricted conditions. Sci Rep. 2019;9:2826. (PMID: 30809004639142610.1038/s41598-019-39479-6) Osman C, Voelker DR, Langer T. Making heads or tails of phospholipids in mitochondria. J Cell Biol. 2011;192:7–16. (PMID: 21220505301956110.1083/jcb.201006159) Unger RH. Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab. 2003;14:398–403. (PMID: 1458075810.1016/j.tem.2003.09.008) Chaurasia B, Summers SA. Ceramides – lipotoxic inducers of metabolic disorders. Trends Endocrinol Metab. 2015;26:538–50. (PMID: 2641215510.1016/j.tem.2015.07.006) Lamari F, Mochel F, Sedel F, Saudubray JM. Disorders of phospholipids, sphingolipids and fatty acids biosynthesis: toward a new category of inherited metabolic diseases. J Inherit Metab Dis. 2013;36:411–25. (PMID: 2281467910.1007/s10545-012-9509-7) Anel A, Naval J, Gonzalez B, Torres JM, Mishal Z, Uriel J, et al. Fatty acid metabolism in human lymphocytes. I. Time-course changes in fatty acid composition and membrane fluidity during blastic transformation of peripheral blood lymphocytes. Biochim Biophys Acta. 1990;1044:323–31. (PMID: 236409710.1016/0005-2760(90)90076-A) Calder PC, Yaqoob P, Harvey DJ, Watts A, Newsholme EA. Incorporation of fatty acids by concanavalin A-stimulated lymphocytes and the effect on fatty acid composition and membrane fluidity. Biochem J. 1994;300:509–18. (PMID: 8002957113819110.1042/bj3000509) Scaglia N, Caviglia JM, Igal RA. High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts. Biochim Biophys Acta. 2005;1687:141–51. (PMID: 1570836210.1016/j.bbalip.2004.11.015) Yahagi N, Shimano H, Hasegawa K, Ohashi K, Matsuzaka T, Najima Y, et al. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma. Eur J Cancer. 2005;41:1316–22. (PMID: 1586987410.1016/j.ejca.2004.12.037) Petersen MC, Shulman GI. Roles of diacylglycerols and ceramides in hepatic insulin resistance. Trends Pharmacol Sci. 2017;38:649–65. (PMID: 28551355549915710.1016/j.tips.2017.04.004) Chaurasia B, Tippetts TS, Mayoral Monibas R, Liu J, Li Y, Wang L, et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science. 2019;365:386–92. (PMID: 31273070678791810.1126/science.aav3722) Dekker MJ, Baker C, Naples M, Samsoondar J, Zhang R, Qiu W, et al. Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: evidence for the role of sphingosine and sphinganine in hepatic VLDL-apoB100 overproduction. Atherosclerosis. 2013;228:98–109. (PMID: 2346607110.1016/j.atherosclerosis.2013.01.041) Glaros EN, Kim WS, Wu BJ, Suarna C, Quinn CM, Rye KA, et al. Inhibition of atherosclerosis by the serine palmitoyl transferase inhibitor myriocin is associated with reduced plasma glycosphingolipid concentration. Biochem Pharmacol. 2007;73:1340–6. (PMID: 1723982410.1016/j.bcp.2006.12.023) Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab. 2007;5:167–79. (PMID: 1733902510.1016/j.cmet.2007.01.002) Gayyed MF, El-Maqsoud NM, Tawfiek ER, El Gelany SA, Rahman MF. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage. Tumour Biol. 2016;37:749–62. (PMID: 2624599010.1007/s13277-015-3808-1) White J, Dalton S. Cell cycle control of embryonic stem cells. Stem Cell Rev. 2005;1:131–8. (PMID: 1714284710.1385/SCR:1:2:131) Jia L, Li B, Yu H. The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation. Nat Commun. 2016;7:10818. (PMID: 26912231477343310.1038/ncomms10818) Siemeister G, Mengel A, Fernandez-Montalvan AE, Bone W, Schroder J, Zitzmann-Kolbe S, et al. Inhibition of BUB1 kinase by BAY 1816032 sensitizes tumor cells toward taxanes, ATR, and PARP inhibitors in vitro and in vivo. Clin Cancer Res. 2019;25:1404–14. (PMID: 3042919910.1158/1078-0432.CCR-18-0628) Wold LE, Hines EA Jr., Allen EV. Lipedema of the legs; a syndrome characterized by fat legs and edema. Ann Intern Med. 1951;34:1243–50. (PMID: 1483010210.7326/0003-4819-34-5-1243) Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28. (PMID: 1130445610.1089/107632701300062859) Lun AT, Chen Y, Smyth GK. It’s DE-licious: a recipe for differential expression analyses of RNA-seq experiments using quasi-likelihood methods in edgeR. Methods Mol Biol. 2016;1418:391–416. (PMID: 2700802510.1007/978-1-4939-3578-9_19) Su S, Law CW, Ah-Cann C, Asselin-Labat ML, Blewitt ME, Ritchie ME. Glimma: interactive graphics for gene expression analysis. Bioinformatics. 2017;33:2050–2. (PMID: 28203714587084510.1093/bioinformatics/btx094) Creek DJ, Jankevics A, Burgess KE, Breitling R, Barrett MP. IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data. Bioinformatics. 2012;28:1048–9. (PMID: 2230814710.1093/bioinformatics/bts069) Gocze PM, Freeman DA. Factors underlying the variability of lipid droplet fluorescence in MA-10 Leydig tumor cells. Cytometry. 1994;17:151–8. (PMID: 783516510.1002/cyto.990170207) |
| المشرفين على المادة: | 0 (Lipids) |
| تواريخ الأحداث: | Date Created: 20211112 Date Completed: 20220425 Latest Revision: 20221027 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8873020 |
| DOI: | 10.1038/s41366-021-01002-1 |
| PMID: | 34764426 |
| قاعدة البيانات: | MEDLINE |
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