Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes

Cell Metabolism

Volumn 24, Issue 4, 2016, Pages 593-607

  Segerstolpe, Åsa ^a   Palasantza, Athanasia ^a   Eliasson, Pernilla ^b   Andersson, Eva Marie ^b   Andréasson, Anne Christine ^b   Sun, Xiaoyan ^a   Picelli, Simone ^c   Sabirsh, Alan ^b   Clausen, Maryam ^b   Bjursell, Magnus K ^b   Smith, David M ^d   Kasper, Maria ^a   Ämmälä, Carina ^b   Sandberg, Rickard ^a,c  

^a KAROLINSKA INSTITUTE   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

^c LUDWIG INSTITUTE FOR CANCER RESEARCH   (Sweden)

^d ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

RNA; TRANSCRIPTOME; GLP1R PROTEIN, HUMAN; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; TRANSCRIPTION FACTOR;

ACINAR CELL; ARTICLE; CELL SUBPOPULATION; CONTROLLED STUDY; ENDOCRINE CELL; EXOCRINE CELL; GENE EXPRESSION; HUMAN; HUMAN TISSUE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PANCREAS ISLET; PANCREAS ISLET DELTA CELL; PRIORITY JOURNAL; RNA SEQUENCE; SINGLE CELL ANALYSIS; STELLATE CELL; DONOR; GENE EXPRESSION PROFILING; GENETICS; MALE; METABOLISM; PATHOLOGY; PROCEDURES; REPRODUCIBILITY;

DIABETES MELLITUS, TYPE 2; GENE EXPRESSION PROFILING; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; HUMANS; ISLETS OF LANGERHANS; MALE; OBESITY; REPRODUCIBILITY OF RESULTS; SINGLE-CELL ANALYSIS; TISSUE DONORS; TRANSCRIPTION FACTORS;

EID: 84992364302     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2016.08.020     Document Type: Article

References (53)

1. Arystarkhova, E., Liu, Y.B., Salazar, C., Stanojevic, V., Clifford, R.J., Kaplan, J.H., Kidder, G.M., Sweadner, K.J., Hyperplasia of pancreatic beta cells and improved glucose tolerance in mice deficient in the FXYD2 subunit of Na,K-ATPase. J. Biol. Chem. 288 (2013), 7077–7085.
2. Benner, C., van der Meulen, T., Cacéres, E., Tigyi, K., Donaldson, C.J., Huising, M.O., The transcriptional landscape of mouse beta cells compared to human beta cells reveals notable species differences in long non-coding RNA and protein-coding gene expression. BMC Genomics, 15, 2014, 620.
3. Blodgett, D.M., Nowosielska, A., Afik, S., Pechhold, S., Cura, A.J., Kennedy, N.J., Kim, S., Kucukural, A., Davis, R.J., Kent, S.C., et al. Novel observations from next-generation RNA sequencing of highly purified human adult and fetal islet cell subsets. Diabetes 64 (2015), 3172–3181.
4. Braks, J.A., Martens, G.J., 7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway. Cell 78 (1994), 263–273.
5. Bramswig, N.C., Everett, L.J., Schug, J., Dorrell, C., Liu, C., Luo, Y., Streeter, P.R., Naji, A., Grompe, M., Kaestner, K.H., Epigenomic plasticity enables human pancreatic α to β cell reprogramming. J. Clin. Invest. 123 (2013), 1275–1284.
6. Brennecke, P., Anders, S., Kim, J.K., Kołodziejczyk, A.A., Zhang, X., Proserpio, V., Baying, B., Benes, V., Teichmann, S.A., Marioni, J.C., Heisler, M.G., Accounting for technical noise in single-cell RNA-seq experiments. Nat. Methods 10 (2013), 1093–1095.
7. Cabrera, O., Berman, D.M., Kenyon, N.S., Ricordi, C., Berggren, P.-O., Caicedo, A., The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc. Natl. Acad. Sci. USA 103 (2006), 2334–2339.
8. Chu, Z.-L., Carroll, C., Alfonso, J., Gutierrez, V., He, H., Lucman, A., Pedraza, M., Mondala, H., Gao, H., Bagnol, D., et al. A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinology 149 (2008), 2038–2047.
9. Collombat, P., Hecksher-Sørensen, J., Krull, J., Berger, J., Riedel, D., Herrera, P.L., Serup, P., Mansouri, A., Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression. J. Clin. Invest. 117 (2007), 961–970.
10. Date, Y., Nakazato, M., Hashiguchi, S., Dezaki, K., Mondal, M.S., Hosoda, H., Kojima, M., Kangawa, K., Arima, T., Matsuo, H., et al. Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes 51 (2002), 124–129.
11. Dorrell, C., Schug, J., Lin, C.F., Canaday, P.S., Fox, A.J., Smirnova, O., Bonnah, R., Streeter, P.R., Stoeckert, C.J. Jr., Kaestner, K.H., Grompe, M., Transcriptomes of the major human pancreatic cell types. Diabetologia 54 (2011), 2832–2844.
12. Eto, K., Tsubamoto, Y., Terauchi, Y., Sugiyama, T., Kishimoto, T., Takahashi, N., Yamauchi, N., Kubota, N., Murayama, S., Aizawa, T., et al. Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science 283 (1999), 981–985.
13. Fasshauer, M., Blüher, M., Adipokines in health and disease. Trends Pharmacol. Sci. 36 (2015), 461–470.
14. Gao, J., Tian, L., Weng, G., O'Brien, T.D., Luo, J., Guo, Z., Stimulating β-cell replication and improving islet graft function by AR231453, A GPR119 agonist. Transplant. Proc. 43 (2011), 3217–3220.
15. Gilon, P., Chae, H.-Y., Rutter, G.A., Ravier, M.A., Calcium signaling in pancreatic β-cells in health and in Type 2 diabetes. Cell Calcium 56 (2014), 340–361.
16. Granata, R., Settanni, F., Biancone, L., Trovato, L., Nano, R., Bertuzzi, F., Destefanis, S., Annunziata, M., Martinetti, M., Catapano, F., et al. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic β-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology 148 (2007), 512–529.
17. Jiang, Z., Song, J., Qi, F., Xiao, A., An, X., Liu, N.-A., Zhu, Z., Zhang, B., Lin, S., Exdpf is a key regulator of exocrine pancreas development controlled by retinoic acid and ptf1a in zebrafish. PLoS Biol., 6, 2008, e293.
18. Kahn, S.E., Hull, R.L., Utzschneider, K.M., Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444 (2006), 840–846.
19. Kambayashi, T., Laufer, T.M., Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?. Nat. Rev. Immunol. 14 (2014), 719–730.
20. Kieffer, T.J., Heller, R.S., Habener, J.F., Leptin receptors expressed on pancreatic beta-cells. Biochem. Biophys. Res. Commun. 224 (1996), 522–527.
21. Kieffer, T.J., Heller, R.S., Leech, C.A., Holz, G.G., Habener, J.F., Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic β-cells. Diabetes 46 (1997), 1087–1093.
22. Klöting, N., Graham, T.E., Berndt, J., Kralisch, S., Kovacs, P., Wason, C.J., Fasshauer, M., Schön, M.R., Stumvoll, M., Blüher, M., Kahn, B.B., Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metab. 6 (2007), 79–87.
23. Ku, G.M., Kim, H., Vaughn, I.W., Hangauer, M.J., Myung Oh, C., German, M.S., McManus, M.T., Research resource: RNA-seq reveals unique features of the pancreatic β-cell transcriptome. Mol. Endocrinol. 26 (2012), 1783–1792.
24. Li, J., Klughammer, J., Farlik, M., Penz, T., Spittler, A., Barbieux, C., Berishvili, E., Bock, C., Kubicek, S., Single-cell transcriptomes reveal characteristic features of human pancreatic islet cell types. EMBO Rep. 17 (2016), 178–187.
25. Ling, F., Kang, B., Sun, X.-H., Id proteins: small molecules, mighty regulators. Curr. Top. Dev. Biol. 110 (2014), 189–216.
26. Liu, Y., Du, L., Role of pancreatic stellate cells and periostin in pancreatic cancer progression. Tumour Biol. 36 (2015), 3171–3177.
27. Montanya, E., A comparison of currently available GLP-1 receptor agonists for the treatment of type 2 diabetes. Expert Opin. Pharmacother. 13 (2012), 1451–1467.
28. Moran, B.M., Abdel-Wahab, Y.H.A., Flatt, P.R., McKillop, A.M., Evaluation of the insulin-releasing and glucose-lowering effects of GPR120 activation in pancreatic β-cells. Diabetes Obes. Metab. 16 (2014), 1128–1139.
29. Nadkarni, P., Chepurny, O.G., Holz, G.G., Regulation of glucose homeostasis by GLP-1. Prog. Mol. Biol. Transl. Sci. 121 (2014), 23–65.
30. Nead, K.T., Li, A., Wehner, M.R., Neupane, B., Gustafsson, S., Butterworth, A., Engert, J.C., Davis, A.D., Hegele, R.A., Miller, R., et al., BioBank Japan, AGEN-BMI, GIANT Consortium. Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331,175 individuals. Hum. Mol. Genet. 24 (2015), 3582–3594.
31. Nica, A.C., Ongen, H., Irminger, J.-C., Bosco, D., Berney, T., Antonarakis, S.E., Halban, P.A., Dermitzakis, E.T., Cell-type, allelic, and genetic signatures in the human pancreatic beta cell transcriptome. Genome Res. 23 (2013), 1554–1562.
32. Odori, S., Hosoda, K., Tomita, T., Fujikura, J., Kusakabe, T., Kawaguchi, Y., Doi, R., Takaori, K., Ebihara, K., Sakai, Y., et al. GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta and alpha cells, and involvement in islet function. Metabolism 62 (2013), 70–78.
33. Picelli, S., Björklund, Å.K., Faridani, O.R., Sagasser, S., Winberg, G., Sandberg, R., Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat. Methods 10 (2013), 1096–1098.
34. Picelli, S., Faridani, O.R., Björklund, Å.K., Winberg, G., Sagasser, S., Sandberg, R., Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9 (2014), 171–181.
35. Pollen, A.A., Nowakowski, T.J., Shuga, J., Wang, X., Leyrat, A.A., Lui, J.H., Li, N., Szpankowski, L., Fowler, B., Chen, P., et al. Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat. Biotechnol. 32 (2014), 1053–1058.
36. Ramsköld, D., Wang, E.T., Burge, C.B., Sandberg, R., An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput. Biol., 5, 2009, e1000598.
37. Ramsköld, D., Luo, S., Wang, Y.-C., Li, R., Deng, Q., Faridani, O.R., Daniels, G.A., Khrebtukova, I., Loring, J.F., Laurent, L.C., et al. Full-length mRNA-seq from single-cell levels of RNA and individual circulating tumor cells. Nat. Biotechnol. 30 (2012), 777–782.
38. Ruiz de Azua, I., Scarselli, M., Rosemond, E., Gautam, D., Jou, W., Gavrilova, O., Ebert, P.J., Levitt, P., Wess, J., RGS4 is a negative regulator of insulin release from pancreatic beta-cells in vitro and in vivo. Proc. Natl. Acad. Sci. USA 107 (2010), 7999–8004.
39. Sandberg, R., Entering the era of single-cell transcriptomics in biology and medicine. Nat. Methods 11 (2014), 22–24.
40. Séron, K., Couturier, C., Belouzard, S., Bacart, J., Monté, D., Corset, L., Bocquet, O., Dam, J., Vauthier, V., Lecœur, C., et al. Endospanins regulate a postinternalization step of the leptin receptor endocytic pathway. J. Biol. Chem. 286 (2011), 17968–17981.
41. Stegle, O., Teichmann, S.A., Marioni, J.C., Computational and analytical challenges in single-cell transcriptomics. Nat. Rev. Genet. 16 (2015), 133–145.
42. Taneera, J., Lang, S., Sharma, A., Fadista, J., Zhou, Y., Ahlqvist, E., Jonsson, A., Lyssenko, V., Vikman, P., Hansson, O., et al. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets. Cell Metab. 16 (2012), 122–134.
43. Touvier, T., Conte-Auriol, F., Briand, O., Cudejko, C., Paumelle, R., Caron, S., Baugé, E., Rouillé, Y., Salles, J.-P., Staels, B., Bailleul, B., LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice. J. Clin. Invest. 119 (2009), 3830–3838.
44. Tudurí, E., Marroquí, L., Soriano, S., Ropero, A.B., Batista, T.M., Piquer, S., López-Boado, M.A., Carneiro, E.M., Gomis, R., Nadal, A., Quesada, I., Inhibitory effects of leptin on pancreatic alpha-cell function. Diabetes 58 (2009), 1616–1624.
45. Van der Maaten, L., Hinton, G., Visualizing data using t-SNE. Journal of Machine Learning. 9 (2008), 2579–2605.
46. van der Meulen, T., Donaldson, C.J., Cáceres, E., Hunter, A.E., Cowing-Zitron, C., Pound, L.D., Adams, M.W., Zembrzycki, A., Grove, K.L., Huising, M.O., Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21 (2015), 769–776.
47. Vauthier, V., Swartz, T.D., Chen, P., Roujeau, C., Pagnon, M., Mallet, J., Sarkis, C., Jockers, R., Dam, J., Endospanin 1 silencing in the hypothalamic arcuate nucleus contributes to sustained weight loss of high fat diet obese mice. Gene Ther. 21 (2014), 638–644.
48. Wang, J., Xu, J., Finnerty, J., Furuta, M., Steiner, D.F., Verchere, C.B., The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site. Diabetes 50 (2001), 534–539.
49. Wang, Y.J., Schug, J., Won, K.-J., Liu, C., Naji, A., Avrahami, D., Golson, M.L., Kaestner, K.H., Single cell transcriptomics of the human endocrine pancreas. Diabetes, 2016, 10.2337/db16-0405 Published online June 30, 2016.
50. Wei, S., Feng, Y., Che, F.-Y., Pan, H., Mzhavia, N., Devi, L.A., McKinzie, A.A., Levin, N., Richards, W.G., Fricker, L.D., Obesity and diabetes in transgenic mice expressing proSAAS. J. Endocrinol. 180 (2004), 357–368.
51. Wetzel, R.K., Pascoa, J.L., Arystarkhova, E., Stress-induced expression of the gamma subunit (FXYD2) modulates Na,K-ATPase activity and cell growth. J. Biol. Chem. 279 (2004), 41750–41757.
52. Wierup, N., Yang, S., McEvilly, R.J., Mulder, H., Sundler, F., Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells. J. Histochem. Cytochem. 52 (2004), 301–310.
53. Yang, Q., Graham, T.E., Mody, N., Preitner, F., Peroni, O.D., Zabolotny, J.M., Kotani, K., Quadro, L., Kahn, B.B., Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436 (2005), 356–362.