snRNA-seq of adipose tissues reveals the potential cellular and molecular mechanisms of cold and disease resistance in Mongolian cattle.
Adipose tissue
Endocrine
Immune
Lipid
Mongolian cattle
Single-nucleus RNA sequencing (snRNA-seq)
Thermogenesis
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
11
05
2024
accepted:
17
10
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Mongolian cattle are local breeds in northern China with excellent adaptability to harsh environmental conditions. Adipose tissues play essential roles in tolerance to cold and disease, but the associated cellular and molecular mechanisms are unclear. Single-nucleus RNA sequencing (snRNA-seq) was performed on the adipose tissues from the subcutaneous (SAT), greater omentum (OAT) and perirenal (PAT) of 3 healthy cattle. The adipogenic trajectory was analyzed, and the functional roles of gene of interest were verified in vitro. There were different cell subpopulations in adipose tissues. The lipid-deposition adipocytes identified by the PTGER3 marker exhibited outstanding characteristics in SAT. In PAT and OAT, aldosterone was expressed to provide clues for the differential brown adipocytes. Among the DEGs by comparing OAT with SAT and PAT with OAT, C3 was significantly expressed in most of the cell populations in SAT. G0S2, LIPE, LPIN1, PTGER3 and RGCC took part in the adipogenic trajectory from preadipocyte commitment to mature adipocytes. S100A4 expression affected Ca The cell heterogeneity and genes expressed in adipose tissues of Mongolian cattle not only determine the endocrine and energy storage, but contribute to adapt to cold and disease resistance.
Sections du résumé
BACKGROUND
BACKGROUND
Mongolian cattle are local breeds in northern China with excellent adaptability to harsh environmental conditions. Adipose tissues play essential roles in tolerance to cold and disease, but the associated cellular and molecular mechanisms are unclear.
METHODS
METHODS
Single-nucleus RNA sequencing (snRNA-seq) was performed on the adipose tissues from the subcutaneous (SAT), greater omentum (OAT) and perirenal (PAT) of 3 healthy cattle. The adipogenic trajectory was analyzed, and the functional roles of gene of interest were verified in vitro.
RESULTS
RESULTS
There were different cell subpopulations in adipose tissues. The lipid-deposition adipocytes identified by the PTGER3 marker exhibited outstanding characteristics in SAT. In PAT and OAT, aldosterone was expressed to provide clues for the differential brown adipocytes. Among the DEGs by comparing OAT with SAT and PAT with OAT, C3 was significantly expressed in most of the cell populations in SAT. G0S2, LIPE, LPIN1, PTGER3 and RGCC took part in the adipogenic trajectory from preadipocyte commitment to mature adipocytes. S100A4 expression affected Ca
CONCLUSION
CONCLUSIONS
The cell heterogeneity and genes expressed in adipose tissues of Mongolian cattle not only determine the endocrine and energy storage, but contribute to adapt to cold and disease resistance.
Identifiants
pubmed: 39448899
doi: 10.1186/s12864-024-10913-y
pii: 10.1186/s12864-024-10913-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
999Informations de copyright
© 2024. The Author(s).
Références
Song B, Di S, Cui S, Chen N, Wang H, Wang X, Gao Q, Tong G, Wang H, Huang X, Ding L, Gao Y, Liu J, Wang X. Distinct patterns of PPARγ promoter usage, lipid degradation activity, and Gene expression in Subcutaneous Adipose tissue of lean and obese Swine. Int J Mol Sci. 2018;19(12):3892–904.
pubmed: 30563100
pmcid: 6321263
doi: 10.3390/ijms19123892
Hausman GJ, Basu U, Wei S, Hausman DB, Dodson MV. Preadipocyte and adipose tissue differentiation in meat animals: influence of species and anatomical location. Annu Rev Anim Biosci. 2014;2(1):323–51.
pubmed: 25384146
doi: 10.1146/annurev-animal-022513-114211
Bluher M. Adipokines—removing road blocks to obesity and diabetes therapy. Mol Metab. 2014;3:230–40.
pubmed: 24749053
pmcid: 3986498
doi: 10.1016/j.molmet.2014.01.005
Sadovsky R. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2004;18(1):41–58.
Friedman JM. Leptin and the Endocrine Control of Energy Balance. Nat Metab. 2019;1(8):754–64.
pubmed: 32694767
doi: 10.1038/s42255-019-0095-y
Larabee CM, Neely OC, Domingos AI, Obesity. A neuroimmunometabolic perspective. Nat Rev Endocrinol. 2020;16(1):30–43.
pubmed: 31776456
doi: 10.1038/s41574-019-0283-6
Cohen P, Kajimura S. The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol. 2021;22(6):393–409.
Mezentseva NV, Kumaratilake JS, Newman SA. The brown adipocyte differentiation pathway in birds: an evolutionary road not taken. BMC Biol. 2008;6:17. https://doi.org/10.1186/1741-7007-6-17 .
Ong WK, Chakraborty S, Sugii S. Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine. Biomolecules. 2021;11(7):918. https://doi.org/10.3390/biom11070918 .
Liu SQ, Chen DY, Li B, Gao ZJ, Feng HF, Yu X, Liu Z, Wang Y, Li WG, Sun S, Sun SR, Wu Q. Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes. J Transl Med. 2023;21(1):470. https://doi.org/10.1186/s12967-023-04256-7 .
Chang E, Varghese M, Singer K. Gender and Sex Differences in Adipose Tissue.Curr Diab Rep. 2018;18(9):69. https://doi.org/10.1007/s11892-018-1031-3 .
Ferrero R, Rainer P, Deplancke B. Toward a Consensus View of mammalian adipocyte stem and progenitor cell heterogeneity. Trends Cell Biol. 2020;30:937–50.
Ishida Y, Mabuchi Y, Naraoka Y, Hisamatsu D, Akazawa C. Conservation of markers and stemness in adipose stem and progenitor cells between cattle and other species. Int J Mol Sci. 2023;24(15):11908.
pubmed: 37569284
pmcid: 10418360
doi: 10.3390/ijms241511908
Sampaio RV, Chiaratti MR, Santos DCN, Bressan FF, Sangalli JR, Sá ALA, Silva TVG, Costa NN, Cordeiro MS, Santos SSD, et al. Generation of bovine (Bos indicus) and Buffalo (Bubalus bubalis) adipose tissue derived stem cells: isolation, characterization, and Multipotentiality. Genet Mol Res. 2015;14:53–62.
pubmed: 25729935
doi: 10.4238/2015.January.15.7
Altun I, Yan X, Ussar S. Immune cell regulation of white adipose progenitor cell fate. Front Endocrinol. 2022;13:859044.
doi: 10.3389/fendo.2022.859044
Ruggiero AD, Key CC, Kavanagh K. Adipose tissue macrophage polarization in healthy and unhealthy obesity. Front Nutr. 2021;8:625331. https://doi.org/10.3389/fnut.2021.625331 .
doi: 10.3389/fnut.2021.625331
pubmed: 33681276
pmcid: 7925825
Hackstein H, Thomson AW. Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat Rev Immunol. 2004;4:24–34.
pubmed: 14704765
doi: 10.1038/nri1256
Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between adipocytes and Immune cells in adipose tissue inflammation and metabolic dysregulation. Obesity. Molecules Cells. 2014;37(5):365–71.
pubmed: 24781408
pmcid: 4044307
doi: 10.14348/molcells.2014.0074
Jager A, Kuchroo VK. Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol. 2010;72:173–84.
doi: 10.1111/j.1365-3083.2010.02432.x
Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411–20.
Hao Y, Hao S, Andersen-Nissen E, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184(13):3573–87.
doi: 10.1016/j.cell.2021.04.048
Cao Y, Wang X, Peng G. SCSA: a cell type annotation tool for single-cell RNA-seq data. Front Genet. 2020;11:490.
pubmed: 32477414
pmcid: 7235421
doi: 10.3389/fgene.2020.00490
Gulati GS, Sikandar SS, Wesche DJ, Manjunath A, Bharadwaj A, Berger MJ, Ilagan F, Kuo AH, Hsieh RW, Cai S, Zabala M, Scheeren FA, Lobo NA, Qian D, Yu FB, Dirbas FM, Clarke MF, Newman AM. Single-cell transcriptional diversity is a hallmark of developmental potential. Science. 2020;367(6476):405–11.
pubmed: 31974247
pmcid: 7694873
doi: 10.1126/science.aax0249
Nadra K, Medard JJ, Mul JD. Cell Autonomous Lipin 1 function is essential for development and maintenance of White and Brown Adipose Tissue. Mol Cell Biol. 2012;32(23):4794–810.
Maniyadath B, Zhang Q, Gupta RK, Mandrup S. Adipose tissue at single-cell resolution. Cell Metab. 2023;35(3):386–413.
Ceddia RP, Lee D, Maulis MF, Carboneau BA, Threadgill DW, Poffenberger G, Milne G, Boyd KL, Powers AC, McGuinness OP, Gannon M, Breyer RM. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice. Endocrinology. 2016;157(1):220–32.
Hildreth AD, Ma F, Wong YY, Sun R, Pellegrini M, O’Sullivan TE. Single-cell sequencing of Human White Adipose tissue identifies New Cell States in Health and obesity. Nat Immunol. 2021;22(5):639–53.
pubmed: 33907320
pmcid: 8102391
doi: 10.1038/s41590-021-00922-4
Singh R, Xiang Y, Wang Y, Baikati K, Cuervo AM, Luu YK, Tang Y, Pessin JE, Schwartz GJ, Czaja MJ. Autophagy regulates adipose mass and differentiation in mice. J Clin Invest. 2009;119:3329–39.
pubmed: 19855132
pmcid: 2769174
Liu G, Li Y, Zhang T, Li M, Li S, He Q, Liu S, Xu M, Xiao T, Shao Z, Shi W, Li W. Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β Cells. Genomics Proteomics Bioinformatics. 2021;19(3):408–22.
Akintola AA, van Heemst D. Insulin, aging, and the brain: mechanisms and implications. Front Endocrinol. 2015;6:13. https://doi.org/10.3389/fendo.2015.00013 .
doi: 10.3389/fendo.2015.00013
Bollag WB. Regulation of Aldosterone Synthesis and. Secretion. Compr Physiol. 2014;4(3):1017–55.
pubmed: 24944029
doi: 10.1002/cphy.c130037
Zennaro MC, Menuet DL, Viengchareun S, Walker F, Ricquier D, Lombè M. Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. J Clin Invest. 1998;101(6):1254–60.
Rondinone CM, Robbard D, Baker ME. Aldosterone stimulates differentiation of mouse 3T3-L1 cells into adipocytes. Endocrinology. 1993;132:2421–6.
pubmed: 8504747
doi: 10.1210/endo.132.6.8504747
Wimmers K, Mekchay S, Schellander K, Ponsuksili S. Molecular characterization of the pig C3 gene and its association with complement activity. Immunogenetics. 2003;54:714–24.
doi: 10.1007/s00251-002-0524-y
Volanakis JE. Transcriptional regulation of complement genes. Annu Rev Immunol. 1995;13:277–305.
pubmed: 7612224
doi: 10.1146/annurev.iy.13.040195.001425
Sacks S, Zhou W, Campbell RD, Martin J. C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells. Clin Experimental Immunol. 1993;93(3):411–7.
doi: 10.1111/j.1365-2249.1993.tb08193.x
Emre Y. Tobias Nübel. Uncoupling protein UCP2: when mitochondrial activity meets immunity. FEBS Lett. 2010;584(8). https://doi.org/10.1016/j.febslet.2010.03.014 .
Nicholls DG. The physiological regulation of uncoupling proteins. Biochim Biophys Acta. 2006;1757:459–66.
pubmed: 16725104
doi: 10.1016/j.bbabio.2006.02.005
Steinbring J, Graja A, Jank AM, Schulz TJ. Flow Cytometric Isolation and Differentiation of Adipogenic Progenitor Cells into Brown and Brite/Beige Adipocytes. Methods Mol Biol. 2017;1566:25. https://doi.org/10.1007/978-1-4939-6820-6_4 .
Nedergaard J, Cannon B. Brown adipose tissue as a heatproducing thermoeffector. Handb Clin Neurol. 2018;156:137–52. https://doi.org/10.1016/B978-0-444-63912-7.00009-6 .
doi: 10.1016/B978-0-444-63912-7.00009-6
pubmed: 30454587
Li J, Jiang R, Cong X, Zhao Y. UCP2 gene polymorphisms in obesity and diabetes, and the role of UCP2 in cancer. FEBS Lett. 2019;593(18). https://doi.org/10.1002/1873-3468.13546 .
Pecqueur C, Bui T, Gelly C, Hauchard J, Barbot C, Bouillaud F, Ricquier D, Miroux B, Thompson CB. Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis- derived pyruvate utilization. FASEB J. 2008;22:9–18.
pubmed: 17855623
doi: 10.1096/fj.07-8945com
Kowalewska-Łuczak I, Głosińska JI. Czerniawska-Piatko-ws- kaE.Efect of UCP2 and UCP3 genes polymorphisms on functional traits in dairy catle. Rusian J Genet. 2018;54(7):853–7.
doi: 10.1134/S1022795418070074
Choi H, Lee H, Kim TH, Kim HJ, Lee YJ, Lee SJ, Yu JH, Kim D, Kim KS, Park SW, Kim JW. G0/G1 switch gene 2 has a critical role in adipocyte differentiation. Cell Death Differ. 2014;21(7):1071–80. https://doi.org/10.1038/cdd.2014.26 .
doi: 10.1038/cdd.2014.26
pubmed: 24583640
pmcid: 4207475
Cerk IK, Salzburger B, Boeszoermenyi A, Heier C, Pillip C, Romauch M, Schweiger M, Cornaciu I, Lass A, Zimmermann R, Zechner R, et al. A peptide derived from G0/G1 switch gene 2 acts as noncompetitive inhibitor of adipose triglyceride lipase. J Biol Chem. 2014;289:32559–70.
pubmed: 25258314
pmcid: 4239610
doi: 10.1074/jbc.M114.602599
Sembongi H, Miranda M, Han GS, Fakas S, Grimsey N, Vendrell J, Carman GM, Siniossoglou S. Distinct roles of the Phosphatidate Phosphatases Lipin 1 and 2 during adipogenesis and lipid Droplet Biogenesis in 3T3-L1 Cells. J Biol Chem. 2013;288(48):34502–13.
pubmed: 24133206
pmcid: 3843065
doi: 10.1074/jbc.M113.488445
Cadoudal T, Distel E, Durant S, Fouque F, Blouin JM, Collinet M, Bortoli S, Forest C, Benelli C. Pyruvate dehydrogenase kinase 4: regulation by thiazolidinediones and implication in glyceroneogenesis in adipose tissue. Diabetes. 2008;57:2272–9.
pubmed: 18519799
pmcid: 2518477
doi: 10.2337/db08-0477
D’ Aquila T, Hung YH, Carreiro A, Buhman KK. Recent discoveries on absorption of dietary fat: presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes. Biochim et biophssica acta. 2016;1861:730–47.
doi: 10.1016/j.bbalip.2016.04.012
Hung Y-H, Carreiro AL, Buhman KK. Dgat1 and Dgat2 regulate enterocyte triacylglycerol distribution and alter proteins associated with cytoplasmic lipid droplets in response to dietary fat. Biochim Biophys Acta. 2017;1862(6):600–14.
pmcid: 5503214
doi: 10.1016/j.bbalip.2017.02.014
Yen C-LE, Stone SJ, Koliwad S, Harris C, Farese RV. Jr. Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res. 2008;49:2283–301.
pubmed: 18757836
pmcid: 3837458
doi: 10.1194/jlr.R800018-JLR200
Kim S, Lim B, Cho J, Lee S, Dang C-G, Jeon J-H, Kim J-M, Lee J. Genome-Wide Identification of Candidate Genes for Milk Production Traits in Korean Holstein Cattle. Animals. 2021;11:1392. https://doi.org/10.3390/ani11051392 .
pubmed: 34068321
pmcid: 8153329
doi: 10.3390/ani11051392
Zammit VA, Buckett LK, Turnbull AV, Wure H, Proven A. Diacylglycerol acyltransferases: Potential roles as pharmacological targets. Pharmacol Ther.2008;118(3):295–302. https://doi.org/10.1016/j.pharmthera.2008.03.010 .
Balogun KA, Cheema SK. Dietary Omega-3 fatty acids prevented adipocyte hypertrophy by downregulating DGAT-2 and FABP-4 in a sex-dependent. Fashion. Lipids. 2016;51(1):25. https://doi.org/10.1007/s11745-015-4105-x .
pubmed: 26662277
doi: 10.1007/s11745-015-4105-x
Stone SJ, Myers HM, Watkins SM, Brown BE, Feingold KR, Elias PM, Farese RV Jr. Lipopenia and skin bar- rier abnormalities in DGAT2-deficient mice. J Biol Chem. 2004;279:11767–76.
pubmed: 14668353
doi: 10.1074/jbc.M311000200
Boord JB, Fazio S, Linton MF. Cytoplasmic fatty acid- binding proteins: emerging roles in metabolism and atheroscle- rosis. Curr Opin Lipidol. 2002;13:141–7.
pubmed: 11891416
doi: 10.1097/00041433-200204000-00005
Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SKSK. Moestrup, identification of the haemoglobin scavenger receptor. Nature. 2001;409(6817):198–201.
pubmed: 11196644
doi: 10.1038/35051594
Rubio-Navarro A, Amaro Villalobos JM, Lindholt JS, Buendía I, Egido J, Blanco-Colio LM, Samaniego R, Meilhac O, Michel JB, Martín-Ventura JL, Moreno JA. Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm. Int J Cardiol. 2015;201:66–78.
Rasouli N, Molavi B, Elbein SC, Kern PA. Ectopic fat accumulation and metabolic syndrome. Diabetes Obes Metab. 2007;9:1–10.
pubmed: 17199713
doi: 10.1111/j.1463-1326.2006.00590.x
Rousset S, Emre Y, Join-Lambert O, Hurtaud C, Ricquier D, Cassard- Doulcier AM. The uncoupling protein 2 modulates the cytokine balance in innate immunity. Cytokine. 2006;35:135–42.
pubmed: 16971137
doi: 10.1016/j.cyto.2006.07.012
Tagen M, Elorza A, Kempuraj D, Boucher W, Kepley CL, Shirihai OS, Theoharides TC. Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. J Immunol. 2009;183:6313–9.
pubmed: 19846869
doi: 10.4049/jimmunol.0803422
Sbierski-Kind J, Goldeck D, Buchmann N, Spranger J, Volk HD, Steinhagen-Thiessen E, Pawelec G, Demuth I, Spira D. T cell phenotypes Associated with insulin resistance: results from the Berlin Aging Study II. Immun Ageing. 2020;17(1):40. https://doi.org/10.1186/s12979-020-00211-y .
pubmed: 33349270
pmcid: 7751110
doi: 10.1186/s12979-020-00211-y
Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M, Blüher M. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299(3):E506–15.
pubmed: 20570822
doi: 10.1152/ajpendo.00586.2009
Carafoli E. Intracellular calcium homeostasis. Annu Rev Biochem. 1987;56:395–433.
pubmed: 3304139
doi: 10.1146/annurev.bi.56.070187.002143
Hayato R, Higure Y, Kuba M, Nagai H, Yamashita H, Kuba K. β3-Adrenergic activation of sequential Ca
Lamounier-Zepter V, Look C, Alvarez J, Christ T, Ravens U, Schunck WH, Ehrhart-Bornstein M, Bornstein SR, Morano I. Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circulation Res. 2009;105(4):326–34.
doi: 10.1161/CIRCRESAHA.109.200501
Iyer A, Lim J, Poudyal H, Reid RC, Suen JY, Webster J, Prins JB, Whitehead JP, Fairlie DP, Brown L. An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against dietinduced metabolic syndrome in rats. Diabetes. 2012;61(9):2320–9.
pubmed: 22923652
pmcid: 3425408
doi: 10.2337/db11-1179
Waldeck-Weiermair M, Malli R, Naghdi S, Trenker M, Kahn MJ, Graier WF. The contribution of UCP2 and UCP3 to mitochondrial ca(2+) uptake is differentially determined by the source of supplied ca(2+). Cell Calcium. 2010;47(5):433–40.
doi: 10.1016/j.ceca.2010.03.004