Glucose transporter 10 modulates adipogenesis via an ascorbic acid-mediated pathway to protect mice against diet-induced metabolic dysregulation
Autoři:
Chung-Lin Jiang aff001; Wei-Ping Jen aff001; Chang-Yu Tsao aff001; Li-Ching Chang aff002; Chien-Hsiun Chen aff002; Yi-Ching Lee aff001
Působiště autorů:
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
aff001; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
aff002
Vyšlo v časopise:
Glucose transporter 10 modulates adipogenesis via an ascorbic acid-mediated pathway to protect mice against diet-induced metabolic dysregulation. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008823
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008823
Souhrn
The development of type 2 diabetes mellitus (T2DM) depends on interactions between genetic and environmental factors, and a better understanding of gene-diet interactions in T2DM will be useful for disease prediction and prevention. Ascorbic acid has been proposed to reduce the risk of T2DM. However, the links between ascorbic acid and metabolic consequences are not fully understood. Here, we report that glucose transporter 10 (GLUT10) maintains intracellular levels of ascorbic acid to promote adipogenesis, white adipose tissue (WAT) development and protect mice from high-fat diet (HFD)-induced metabolic dysregulation. We found genetic polymorphisms in SLC2A10 locus are suggestively associated with a T2DM intermediate phenotype in non-diabetic Han Taiwanese. Additionally, mice carrying an orthologous human Glut10G128E variant (Glut10G128E mice) with compromised GLUT10 function have reduced adipogenesis, reduced WAT development and increased susceptibility to HFD-induced metabolic dysregulation. We further demonstrate that GLUT10 is highly expressed in preadipocytes, where it regulates intracellular ascorbic acid levels and adipogenesis. In this context, GLUT10 increases ascorbic acid-dependent DNA demethylation and the expression of key adipogenic genes, Cebpa and Pparg. Together, our data show GLUT10 regulates adipogenesis via ascorbic acid-dependent DNA demethylation to benefit proper WAT development and protect mice against HFD-induced metabolic dysregulation. Our findings suggest that SLC2A10 may be an important HFD-associated susceptibility locus for T2DM.
Klíčová slova:
Adipocytes – Adipokines – Adiponectin – Cell differentiation – Gene expression – Inflammation – Type 2 diabetes – vitamin C
Zdroje
1. Replication DIG, Meta-analysis C, Asian Genetic Epidemiology Network Type 2 Diabetes C, South Asian Type 2 Diabetes C, Mexican American Type 2 Diabetes C, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples C, et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet. 2014;46(3):234–44. doi: 10.1038/ng.2897 24509480; PubMed Central PMCID: PMC3969612.
2. Scott RA, Scott LJ, Magi R, Marullo L, Gaulton KJ, Kaakinen M, et al. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. Diabetes. 2017;66(11):2888–902. Epub 2017/06/02. doi: 10.2337/db16-1253 28566273; PubMed Central PMCID: PMC5652602.
3. Bonnefond A, Clement N, Fawcett K, Yengo L, Vaillant E, Guillaume JL, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44(3):297–301. Epub 2012/01/31. doi: 10.1038/ng.1053 22286214; PubMed Central PMCID: PMC3773908.
4. Majithia AR, Flannick J, Shahinian P, Guo M, Bray MA, Fontanillas P, et al. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes. Proc Natl Acad Sci U S A. 2014;111(36):13127–32. Epub 2014/08/27. doi: 10.1073/pnas.1410428111 25157153; PubMed Central PMCID: PMC4246964.
5. Flannick J, Thorleifsson G, Beer NL, Jacobs SB, Grarup N, Burtt NP, et al. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet. 2014;46(4):357–63. Epub 2014/03/04. doi: 10.1038/ng.2915 24584071; PubMed Central PMCID: PMC4051628.
6. Garcia-Diaz DF, Lopez-Legarrea P, Quintero P, Martinez JA. Vitamin C in the treatment and/or prevention of obesity. J Nutr Sci Vitaminol (Tokyo). 2014;60(6):367–79. Epub 2014/01/01. doi: 10.3177/jnsv.60.367 25866299.
7. Canoy D, Wareham N, Welch A, Bingham S, Luben R, Day N, et al. Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study. Am J Clin Nutr. 2005;82(6):1203–9. Epub 2005/12/08. doi: 10.1093/ajcn/82.6.1203 16332652.
8. Johnston CS, Beezhold BL, Mostow B, Swan PD. Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in nonsmoking adults. J Nutr. 2007;137(7):1757–62. Epub 2007/06/23. doi: 10.1093/jn/137.7.1757 17585027.
9. Garcia OP, Ronquillo D, Caamano Mdel C, Camacho M, Long KZ, Rosado JL. Zinc, vitamin A, and vitamin C status are associated with leptin concentrations and obesity in Mexican women: results from a cross-sectional study. Nutr Metab (Lond). 2012;9(1):59. Epub 2012/06/19. doi: 10.1186/1743-7075-9-59 22703731; PubMed Central PMCID: PMC3406981.
10. Taylor AE, Ebrahim S, Ben-Shlomo Y, Martin RM, Whincup PH, Yarnell JW, et al. Comparison of the associations of body mass index and measures of central adiposity and fat mass with coronary heart disease, diabetes, and all-cause mortality: a study using data from 4 UK cohorts. Am J Clin Nutr. 2010;91(3):547–56. Epub 2010/01/22. doi: 10.3945/ajcn.2009.28757 20089729.
11. Campion J, Milagro FI, Fernandez D, Martinez JA. Diferential gene expression and adiposity reduction induced by ascorbic acid supplementation in a cafeteria model of obesity. J Physiol Biochem. 2006;62(2):71–80. Epub 2007/01/16. doi: 10.1007/BF03174068 17217161.
12. Lykkesfeldt J, Poulsen HE. Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials. Br J Nutr. 2010;103(9):1251–9. doi: 10.1017/S0007114509993229 20003627.
13. Kuiper C, Vissers MC. Ascorbate as a co-factor for fe- and 2-oxoglutarate dependent dioxygenases: physiological activity in tumor growth and progression. Front Oncol. 2014;4:359. Epub 2014/12/30. doi: 10.3389/fonc.2014.00359 25540771; PubMed Central PMCID: PMC4261134.
14. Banhegyi G, Benedetti A, Margittai E, Marcolongo P, Fulceri R, Nemeth CE, et al. Subcellular compartmentation of ascorbate and its variation in disease states. Biochim Biophys Acta. 2014;1843(9):1909–16. doi: 10.1016/j.bbamcr.2014.05.016 24907663.
15. Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38(4):452–7. doi: 10.1038/ng1764 16550171.
16. Lee YC, Huang HY, Chang CJ, Cheng CH, Chen YT. Mitochondrial GLUT10 facilitates dehydroascorbic acid import and protects cells against oxidative stress: mechanistic insight into arterial tortuosity syndrome. Hum Mol Genet. 2010;19(19):3721–33. Epub 2010/07/20. ddq286 [pii] doi: 10.1093/hmg/ddq286 20639396.
17. Zoppi N, Chiarelli N, Cinquina V, Ritelli M, Colombi M. GLUT10 deficiency leads to oxidative stress and non-canonical alphavbeta3 integrin-mediated TGFbeta signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts. Hum Mol Genet. 2015. doi: 10.1093/hmg/ddv382 26376865.
18. Nemeth CE, Marcolongo P, Gamberucci A, Fulceri R, Benedetti A, Zoppi N, et al. Glucose transporter type 10—lacking in arterial tortuosity syndrome—facilitates dehydroascorbic acid transport. FEBS Lett. 2016. doi: 10.1002/1873-3468.12204 27153185.
19. Gamberucci A, Marcolongo P, Nemeth CE, Zoppi N, Szarka A, Chiarelli N, et al. GLUT10-Lacking in Arterial Tortuosity Syndrome-Is Localized to the Endoplasmic Reticulum of Human Fibroblasts. Int J Mol Sci. 2017;18(8). Epub 2017/08/23. doi: 10.3390/ijms18081820 28829359; PubMed Central PMCID: PMC5578206.
20. Syu YW, Lai HW, Jiang CL, Tsai HY, Lin CC, Lee YC. GLUT10 maintains the integrity of major arteries through regulation of redox homeostasis and mitochondrial function. Hum Mol Genet. 2018;27(2):307–21. doi: 10.1093/hmg/ddx401 29149261.
21. Willaert A, Khatri S, Callewaert BL, Coucke PJ, Crosby SD, Lee JG, et al. GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFbeta signaling. Hum Mol Genet. 2012;21(6):1248–59. doi: 10.1093/hmg/ddr555 22116938; PubMed Central PMCID: PMC3284116.
22. Ghosh S, Watanabe RM, Hauser ER, Valle T, Magnuson VL, Erdos MR, et al. Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs. Proc Natl Acad Sci U S A. 1999;96(5):2198–203. doi: 10.1073/pnas.96.5.2198 10051618; PubMed Central PMCID: PMC26760.
23. Zouali H, Hani EH, Philippi A, Vionnet N, Beckmann JS, Demenais F, et al. A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene. Hum Mol Genet. 1997;6(9):1401–8. doi: 10.1093/hmg/6.9.1401 9285775.
24. Andersen G, Rose CS, Hamid YH, Drivsholm T, Borch-Johnsen K, Hansen T, et al. Genetic variation of the GLUT10 glucose transporter (SLC2A10) and relationships to type 2 diabetes and intermediary traits. Diabetes. 2003;52(9):2445–8. Epub 2003/08/28. doi: 10.2337/diabetes.52.9.2445 12941788.
25. Bento JL, Bowden DW, Mychaleckyj JC, Hirakawa S, Rich SS, Freedman BI, et al. Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes. BMC Med Genet. 2005;6:42. doi: 10.1186/1471-2350-6-42 16336637.
26. Mohlke KL, Skol AD, Scott LJ, Valle TT, Bergman RN, Tuomilehto J, et al. Evaluation of SLC2A10 (GLUT10) as a candidate gene for type 2 diabetes and related traits in Finns. Mol Genet Metab. 2005;85(4):323–7. doi: 10.1016/j.ymgme.2005.04.011 15936967.
27. Rose CS, Andersen G, Hamid YH, Glumer C, Drivsholm T, Borch-Johnsen K, et al. Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired insulin secretion. Diabet Med. 2005;22(7):946–9. doi: 10.1111/j.1464-5491.2005.01547.x 15975113.
28. Lin WH, Chuang LM, Chen CH, Yeh JI, Hsieh PS, Cheng CH, et al. Association study of genetic polymorphisms of SLC2A10 gene and type 2 diabetes in the Taiwanese population. Diabetologia. 2006;49(6):1214–21. doi: 10.1007/s00125-006-0218-3 16586067.
29. Jiang YD, Chang YC, Chiu YF, Chang TJ, Li HY, Lin WH, et al. SLC2A10 genetic polymorphism predicts development of peripheral arterial disease in patients with type 2 diabetes. SLC2A10 and PAD in type 2 diabetes. BMC Med Genet. 2010;11:126. doi: 10.1186/1471-2350-11-126 20735855; PubMed Central PMCID: PMC2939510.
30. Wood IS, Hunter L, Trayhurn P. Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues. Biochem Biophys Res Commun. 2003;308(1):43–9. doi: 10.1016/s0006-291x(03)01322-6 12890477.
31. Lago F, Dieguez C, Gomez-Reino J, Gualillo O. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol. 2007;3(12):716–24. doi: 10.1038/ncprheum0674 18037931.
32. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42(2):105–16. Epub 2010/01/19. doi: 10.1038/ng.520 20081858; PubMed Central PMCID: PMC3018764.
33. Florkowski C. HbA1c as a Diagnostic Test for Diabetes Mellitus—Reviewing the Evidence. Clin Biochem Rev. 2013;34(2):75–83. Epub 2013/10/24. 24151343; PubMed Central PMCID: PMC3799221.
34. Halperin E, Stephan DA. SNP imputation in association studies. Nat Biotechnol. 2009;27(4):349–51. Epub 2009/04/09. doi: 10.1038/nbt0409-349 19352374.
35. Chen P, Takeuchi F, Lee JY, Li H, Wu JY, Liang J, et al. Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians. Diabetes. 2014;63(7):2551–62. Epub 2014/03/22. doi: 10.2337/db13-1815 24647736; PubMed Central PMCID: PMC4284402.
36. Cheng CH, Kikuchi T, Chen YH, Sabbagha NG, Lee YC, Pan HJ, et al. Mutations in the SLC2A10 gene cause arterial abnormalities in mice. Cardiovasc Res. 2009;81(2):381–8. doi: 10.1093/cvr/cvn319 19028722.
37. Lancha A, Fruhbeck G, Gomez-Ambrosi J. Peripheral signalling involved in energy homeostasis control. Nutr Res Rev. 2012;25(2):223–48. Epub 2012/11/24. doi: 10.1017/S0954422412000145 23174510.
38. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121(6):2094–101. Epub 2011/06/03. doi: 10.1172/JCI45887 21633177; PubMed Central PMCID: PMC3104761.
39. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–46. Epub 2010/02/13. doi: 10.1146/annurev-physiol-021909-135846 20148674.
40. Suganami T, Tanaka M, Ogawa Y. Adipose tissue inflammation and ectopic lipid accumulation. Endocr J. 2012;59(10):849–57. Epub 2012/08/11. doi: 10.1507/endocrj.ej12-0271 22878669.
41. Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, et al. White fat progenitor cells reside in the adipose vasculature. Science. 2008;322(5901):583–6. doi: 10.1126/science.1156232 18801968; PubMed Central PMCID: PMC2597101.
42. Blaschke K, Ebata KT, Karimi MM, Zepeda-Martinez JA, Goyal P, Mahapatra S, et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013;500(7461):222–6. doi: 10.1038/nature12362 23812591; PubMed Central PMCID: PMC3893718.
43. Chen J, Guo L, Zhang L, Wu H, Yang J, Liu H, et al. Vitamin C modulates TET1 function during somatic cell reprogramming. Nat Genet. 2013;45(12):1504–9. Epub 2013/10/29. doi: 10.1038/ng.2807 24162740.
44. Monfort A, Wutz A. Breathing-in epigenetic change with vitamin C. EMBO Rep. 2013;14(4):337–46. doi: 10.1038/embor.2013.29 23492828; PubMed Central PMCID: PMC3615655.
45. Young JI, Zuchner S, Wang G. Regulation of the Epigenome by Vitamin C. Annu Rev Nutr. 2015;35:545–64. doi: 10.1146/annurev-nutr-071714-034228 25974700; PubMed Central PMCID: PMC4506708.
46. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006;7(12):885–96. doi: 10.1038/nrm2066 17139329.
47. Ngo S, Li X, O'Neill R, Bhoothpur C, Gluckman P, Sheppard A. Elevated S-adenosylhomocysteine alters adipocyte functionality with corresponding changes in gene expression and associated epigenetic marks. Diabetes. 2014;63(7):2273–83. Epub 2014/02/28. doi: 10.2337/db13-1640 24574043.
48. Yoo Y, Park JH, Weigel C, Liesenfeld DB, Weichenhan D, Plass C, et al. TET-mediated hydroxymethylcytosine at the Ppargamma locus is required for initiation of adipogenic differentiation. Int J Obes (Lond). 2017;41(4):652–9. Epub 2017/01/20. doi: 10.1038/ijo.2017.8 28100914.
49. Flannick J, Florez JC. Type 2 diabetes: genetic data sharing to advance complex disease research. Nat Rev Genet. 2016;17(9):535–49. Epub 2016/07/13. doi: 10.1038/nrg.2016.56 27402621.
50. Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K, Albrecht B, et al. Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families. Hum Mutat. 2008;29(1):150–8. doi: 10.1002/humu.20623 17935213.
51. Ritelli M, Chiarelli N, Dordoni C, Reffo E, Venturini M, Quinzani S, et al. Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review. BMC Med Genet. 2014;15:122. doi: 10.1186/s12881-014-0122-5 25373504; PubMed Central PMCID: PMC4412100.
52. Beyens A, Albuisson J, Boel A, Al-Essa M, Al-Manea W, Bonnet D, et al. Arterial tortuosity syndrome: 40 new families and literature review. Genet Med. 2018;20(10):1236–45. Epub 2018/01/13. doi: 10.1038/gim.2017.253 29323665.
53. Wessels MW, Catsman-Berrevoets CE, Mancini GM, Breuning MH, Hoogeboom JJ, Stroink H, et al. Three new families with arterial tortuosity syndrome. Am J Med Genet A. 2004;131(2):134–43. doi: 10.1002/ajmg.a.30272 15529317.
54. Franceschini P, Guala A, Licata D, Di Cara G, Franceschini D. Arterial tortuosity syndrome. Am J Med Genet. 2000;91(2):141–3. Epub 2000/04/05. 10748415.
55. Drera B, Guala A, Zoppi N, Gardella R, Franceschini P, Barlati S, et al. Two novel SLC2A10/GLUT10 mutations in a patient with arterial tortuosity syndrome. Am J Med Genet A. 2007;143A(2):216–8. Epub 2006/12/14. doi: 10.1002/ajmg.a.31514 17163528.
56. Huang-Doran I, Sleigh A, Rochford JJ, O'Rahilly S, Savage DB. Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol. 2010;207(3):245–55. Epub 2010/09/28. doi: 10.1677/JOE-10-0272 20870709.
57. Fiorenza CG, Chou SH, Mantzoros CS. Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011;7(3):137–50. doi: 10.1038/nrendo.2010.199 21079616; PubMed Central PMCID: PMC3150735.
58. Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, et al. New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int. 2014;2014:658913. Epub 2014/08/12. doi: 10.1155/2014/658913 25110685; PubMed Central PMCID: PMC4109424.
59. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J. 2004;68(11):975–81. Epub 2004/10/27. doi: 10.1253/circj.68.975 15502375.
60. Simons PJ, van den Pangaart PS, Aerts JM, Boon L. Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization. J Endocrinol. 2007;192(2):289–99. Epub 2007/02/07. doi: 10.1677/JOE-06-0047 17283229.
61. Reilly SM, Saltiel AR. Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol. 2017;13(11):633–43. Epub 2017/08/12. doi: 10.1038/nrendo.2017.90 28799554.
62. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7. doi: 10.1038/nature05485 17167474.
63. Malandrino MI, Fucho R, Weber M, Calderon-Dominguez M, Mir JF, Valcarcel L, et al. Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation. Am J Physiol Endocrinol Metab. 2015;308(9):E756–69. Epub 2015/02/26. doi: 10.1152/ajpendo.00362.2014 25714670.
64. Patel P, Abate N. Role of subcutaneous adipose tissue in the pathogenesis of insulin resistance. J Obes. 2013;2013:489187. Epub 2013/05/22. doi: 10.1155/2013/489187 23691287; PubMed Central PMCID: PMC3649613.
65. Shi DQ, Ali I, Tang J, Yang WC. New Insights into 5hmC DNA Modification: Generation, Distribution and Function. Front Genet. 2017;8:100. Epub 2017/08/05. doi: 10.3389/fgene.2017.00100 28769976; PubMed Central PMCID: PMC5515870.
66. Cuaranta-Monroy I, Simandi Z, Kolostyak Z, Doan-Xuan QM, Poliska S, Horvath A, et al. Highly efficient differentiation of embryonic stem cells into adipocytes by ascorbic acid. Stem Cell Res. 2014;13(1):88–97. Epub 2014/05/27. doi: 10.1016/j.scr.2014.04.015 24858493.
67. De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T. Mitochondrial (dys)function in adipocyte (de)differentiation and systemic metabolic alterations. Am J Pathol. 2009;175(3):927–39. doi: 10.2353/ajpath.2009.081155 19700756; PubMed Central PMCID: PMC2731113.
68. Koh EH, Park JY, Park HS, Jeon MJ, Ryu JW, Kim M, et al. Essential role of mitochondrial function in adiponectin synthesis in adipocytes. Diabetes. 2007;56(12):2973–81. Epub 2007/09/11. doi: 10.2337/db07-0510 17827403.
69. Huh JY, Kim Y, Jeong J, Park J, Kim I, Huh KH, et al. Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression. Antioxid Redox Signal. 2012;16(3):229–43. Epub 2011/09/10. doi: 10.1089/ars.2011.3952 21902452; PubMed Central PMCID: PMC3234662.
70. Kusminski CM, Scherer PE. Mitochondrial dysfunction in white adipose tissue. Trends Endocrinol Metab. 2012;23(9):435–43. doi: 10.1016/j.tem.2012.06.004 22784416; PubMed Central PMCID: PMC3430798.
71. Garfield AS. Derivation of primary mouse embryonic fibroblast (PMEF) cultures. Methods Mol Biol. 2010;633:19–27. Epub 2010/03/06. doi: 10.1007/978-1-59745-019-5_2 20204617.
Článek vyšel v časopise
PLOS Genetics
2020 Číslo 5
- Distribuce a lokalizace speciálně upravených exosomů může zefektivnit léčbu svalových dystrofií
- Prof. Jan Škrha: Metformin je bezpečný, ale je třeba jej bezpečně užívat a léčbu kontrolovat
- FDA varuje před selfmonitoringem cukru pomocí chytrých hodinek. Jak je to v Česku?
- Masturbační chování žen v ČR − dotazníková studie
- O krok blíže k pochopení efektu placeba při léčbě bolesti
Nejčtenější v tomto čísle
- The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2)
- Polyploidy breaks speciation barriers in Australian burrowing frogs Neobatrachus
- The phosphorelay BarA/SirA activates the non-cognate regulator RcsB in Salmonella enterica
- Congenital hearing impairment associated with peripheral cochlear nerve dysmyelination in glycosylation-deficient muscular dystrophy