Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas

Cell Metabolism

Volumn 24, Issue 4, 2016, Pages 616-626

  Wang, Yue J ^a   Golson, Maria L ^a   Schug, Jonathan ^a   Traum, Daniel ^b   Liu, Chengyang ^a   Vivek, Kumar ^c   Dorrell, Craig ^d   Naji, Ali ^a   Powers, Alvin C ^e,f   Chang, Kyong Mi ^b   Grompe, Markus ^d   Kaestner, Klaus H ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^e VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f DEPARTMENT OF VETERANS AFFAIRS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HARMINE; PANCREAS HORMONE;

ADULT; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOMETRY; ENDOCRINE CELL; ENDOCRINE PANCREAS; FEMALE; HUMAN; HUMAN CELL; MALE; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; SINGLE CELL ANALYSIS; CELL AGGREGATION; CYTOLOGY; DRUG EFFECTS; FLOW CYTOMETRY; METABOLISM; PANCREAS ISLET; PROCEDURES;

CELL AGGREGATION; CELL PROLIFERATION; FLOW CYTOMETRY; HARMINE; HUMANS; ISLETS OF LANGERHANS; SINGLE-CELL ANALYSIS;

EID: 84992397313     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2016.09.007     Document Type: Article

References (64)

1. Amir, A.D., Davis, K.L., Tadmor, M.D., Simonds, E.F., Levine, J.H., Bendall, S.C., Shenfeld, D.K., Krishnaswamy, S., Nolan, G.P., Pe'er, D., viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat. Biotechnol. 31 (2013), 545–552.
2. Andralojc, K.M., Mercalli, A., Nowak, K.W., Albarello, L., Calcagno, R., Luzi, L., Bonifacio, E., Doglioni, C., Piemonti, L., Ghrelin-producing epsilon cells in the developing and adult human pancreas. Diabetologia 52 (2009), 486–493.
3. Atkinson, M.A., von Herrath, M., Powers, A.C., Clare-Salzler, M., Current concepts on the pathogenesis of type 1 diabetes–considerations for attempts to prevent and reverse the disease. Diabetes Care 38 (2015), 979–988.
4. Balcazar, N., Sathyamurthy, A., Elghazi, L., Gould, A., Weiss, A., Shiojima, I., Walsh, K., Bernal-Mizrachi, E., mTORC1 activation regulates beta-cell mass and proliferation by modulation of cyclin D2 synthesis and stability. J. Biol. Chem. 284 (2009), 7832–7842.
5. Bandura, D.R., Baranov, V.I., Ornatsky, O.I., Antonov, A., Kinach, R., Lou, X., Pavlov, S., Vorobiev, S., Dick, J.E., Tanner, S.D., Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal. Chem. 81 (2009), 6813–6822.
6. Bendall, S.C., Simonds, E.F., Qiu, P., Amir, A.D., Krutzik, P.O., Finck, R., Bruggner, R.V., Melamed, R., Trejo, A., Ornatsky, O.I., et al. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332 (2011), 687–696.
7. Bernal-Mizrachi, E., Kulkarni, R.N., Scott, D.K., Mauvais-Jarvis, F., Stewart, A.F., Garcia-Ocaña, A., Human β-cell proliferation and intracellular signaling part 2: still driving in the dark without a road map. Diabetes 63 (2014), 819–831.
8. 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.
9. Bodenmiller, B., Zunder, E.R., Finck, R., Chen, T.J., Savig, E.S., Bruggner, R.V., Simonds, E.F., Bendall, S.C., Sachs, K., Krutzik, P.O., Nolan, G.P., Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators. Nat. Biotechnol. 30 (2012), 858–867.
10. 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.
11. Brissova, M., Fowler, M.J., Nicholson, W.E., Chu, A., Hirshberg, B., Harlan, D.M., Powers, A.C., Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J. Histochem. Cytochem. 53 (2005), 1087–1097.
12. Buenrostro, J.D., Wu, B., Litzenburger, U.M., Ruff, D., Gonzales, M.L., Snyder, M.P., Chang, H.Y., Greenleaf, W.J., Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523 (2015), 486–490.
13. Butler, A.E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R.A., Butler, P.C., Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52 (2003), 102–110.
14. 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.
15. Chen, H., Gu, X., Liu, Y., Wang, J., Wirt, S.E., Bottino, R., Schorle, H., Sage, J., Kim, S.K., PDGF signalling controls age-dependent proliferation in pancreatic β-cells. Nature 478 (2011), 349–355.
16. Cnop, M., Hughes, S.J., Igoillo-Esteve, M., Hoppa, M.B., Sayyed, F., van de Laar, L., Gunter, J.H., de Koning, E.J., Walls, G.V., Gray, D.W., et al. The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation. Diabetologia 53 (2010), 321–330.
17. Collombat, P., Xu, X., Ravassard, P., Sosa-Pineda, B., Dussaud, S., Billestrup, N., Madsen, O.D., Serup, P., Heimberg, H., Mansouri, A., The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell 138 (2009), 449–462.
18. Cribari-Neto, F., Zeileis, A., Beta Regression in R. J. Stat. Softw. 34 (2010), 1–24.
19. Dabernat, S., Secrest, P., Peuchant, E., Moreau-Gaudry, F., Dubus, P., Sarvetnick, N., Lack of beta-catenin in early life induces abnormal glucose homeostasis in mice. Diabetologia 52 (2009), 1608–1617.
20. Davey, H.M., Kell, D.B., Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses. Microbiol. Rev. 60 (1996), 641–696.
21. Dorrell, C., Schug, J., Canaday, P.S., Russ, H.A., Tarlow, B.D., Grompe, M.T., Horton, T., Hebrok, M., Streeter, P.R., Kaestner, K.H., Grompe, M., Human islets contain four distinct subtypes of β cells. Nat. Commun., 7, 2016, 11756.
22. Fienberg, H.G., Simonds, E.F., Fantl, W.J., Nolan, G.P., Bodenmiller, B., A platinum-based covalent viability reagent for single-cell mass cytometry. Cytometry A 81 (2012), 467–475.
23. Finck, R., Simonds, E.F., Jager, A., Krishnaswamy, S., Sachs, K., Fantl, W., Pe'er, D., Nolan, G.P., Bendall, S.C., Normalization of mass cytometry data with bead standards. Cytometry A 83 (2013), 483–494.
24. Gregg, B.E., Moore, P.C., Demozay, D., Hall, B.A., Li, M., Husain, A., Wright, A.J., Atkinson, M.A., Rhodes, C.J., Formation of a human β-cell population within pancreatic islets is set early in life. J. Clin. Endocrinol. Metab. 97 (2012), 3197–3206.
25. Horowitz, A., Strauss-Albee, D.M., Leipold, M., Kubo, J., Nemat-Gorgani, N., Dogan, O.C., Dekker, C.L., Mackey, S., Maecker, H., Swan, G.E., et al. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci. Transl. Med., 5, 2013, 208ra145.
26. Hussain, M.A., Porras, D.L., Rowe, M.H., West, J.R., Song, W.J., Schreiber, W.E., Wondisford, F.E., Increased pancreatic beta-cell proliferation mediated by CREB binding protein gene activation. Mol. Cell. Biol. 26 (2006), 7747–7759.
27. Jackerott, M., Møldrup, A., Thams, P., Galsgaard, E.D., Knudsen, J., Lee, Y.C., Nielsen, J.H., STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes. Diabetes 55 (2006), 2705–2712.
28. Jhala, U.S., Canettieri, G., Screaton, R.A., Kulkarni, R.N., Krajewski, S., Reed, J., Walker, J., Lin, X., White, M., Montminy, M., cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev. 17 (2003), 1575–1580.
29. Jho, E.H., Zhang, T., Domon, C., Joo, C.K., Freund, J.N., Costantini, F., Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell. Biol. 22 (2002), 1172–1183.
30. Kassem, S.A., Ariel, I., Thornton, P.S., Scheimberg, I., Glaser, B., Beta-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy. Diabetes 49 (2000), 1325–1333.
31. Kiekens, R., In't Veld, P., Mahler, T., Schuit, F., Van De Winkel, M., Pipeleers, D., Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity. J. Clin. Invest. 89 (1992), 117–125.
32. Li, C., Heidt, D.G., Dalerba, P., Burant, C.F., Zhang, L., Adsay, V., Wicha, M., Clarke, M.F., Simeone, D.M., Identification of pancreatic cancer stem cells. Cancer Res. 67 (2007), 1030–1037.
33. Loudig, O., Maclean, G.A., Dore, N.L., Luu, L., Petkovich, M., Transcriptional co-operativity between distant retinoic acid response elements in regulation of Cyp26A1 inducibility. Biochem. J. 392 (2005), 241–248.
34. Maaten, L., Hinton, G., Visualizing Data using t-SNE. J. Mach. Learn. Res. 9 (2008), 2579–2605.
35. Meier, J.J., Butler, A.E., Saisho, Y., Monchamp, T., Galasso, R., Bhushan, A., Rizza, R.A., Butler, P.C., Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 57 (2008), 1584–1594.
36. Micallef, S.J., Janes, M.E., Knezevic, K., Davis, R.P., Elefanty, A.G., Stanley, E.G., Retinoic acid induces Pdx1-positive endoderm in differentiating mouse embryonic stem cells. Diabetes 54 (2005), 301–305.
37. Newell, E.W., Sigal, N., Bendall, S.C., Nolan, G.P., Davis, M.M., Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36 (2012), 142–152.
38. Nielsen, J.H., Galsgaard, E.D., Møldrup, A., Friedrichsen, B.N., Billestrup, N., Hansen, J.A., Lee, Y.C., Carlsson, C., Regulation of beta-cell mass by hormones and growth factors. Diabetes 50:Suppl 1 (2001), S25–S29.
39. Ornatsky, O.I., Lou, X., Nitz, M., Schäfer, S., Sheldrick, W.S., Baranov, V.I., Bandura, D.R., Tanner, S.D., Study of cell antigens and intracellular DNA by identification of element-containing labels and metallointercalators using inductively coupled plasma mass spectrometry. Anal. Chem. 80 (2008), 2539–2547.
40. Ornatsky, O., Bandura, D., Baranov, V., Nitz, M., Winnik, M.A., Tanner, S., Highly multiparametric analysis by mass cytometry. J. Immunol. Methods 361 (2010), 1–20.
41. Oström, M., Loffler, K.A., Edfalk, S., Selander, L., Dahl, U., Ricordi, C., Jeon, J., Correa-Medina, M., Diez, J., Edlund, H., Retinoic acid promotes the generation of pancreatic endocrine progenitor cells and their further differentiation into beta-cells. PLoS ONE, 3, 2008, e2841.
42. Perfetto, S.P., Chattopadhyay, P.K., Roederer, M., Seventeen-colour flow cytometry: unravelling the immune system. Nat. Rev. Immunol. 4 (2004), 648–655.
43. Perl, S., Kushner, J.A., Buchholz, B.A., Meeker, A.K., Stein, G.M., Hsieh, M., Kirby, M., Pechhold, S., Liu, E.H., Harlan, D.M., Tisdale, J.F., Significant human beta-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating. J. Clin. Endocrinol. Metab. 95 (2010), E234–E239.
44. Rahier, J., Wallon, J., Henquin, J.C., Cell populations in the endocrine pancreas of human neonates and infants. Diabetologia 20 (1981), 540–546.
45. Reers, C., Erbel, S., Esposito, I., Schmied, B., Büchler, M.W., Nawroth, P.P., Ritzel, R.A., Impaired islet turnover in human donor pancreata with aging. Eur. J. Endocrinol. 160 (2009), 185–191.
46. Rulifson, I.C., Karnik, S.K., Heiser, P.W., ten Berge, D., Chen, H., Gu, X., Taketo, M.M., Nusse, R., Hebrok, M., Kim, S.K., Wnt signaling regulates pancreatic beta cell proliferation. Proc. Natl. Acad. Sci. USA 104 (2007), 6247–6252.
47. Saxena, N.K., Vertino, P.M., Anania, F.A., Sharma, D., leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. J. Biol. Chem. 282 (2007), 13316–13325.
48. Schuit, F.C., In't Veld, P.A., Pipeleers, D.G., Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells. Proc. Natl. Acad. Sci. USA 85 (1988), 3865–3869.
49. Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445 (2007), 881–885.
50. Stefan, Y., Orci, L., Malaisse-Lagae, F., Perrelet, A., Patel, Y., Unger, R.H., Quantitation of endocrine cell content in the pancreas of nondiabetic and diabetic humans. Diabetes 31 (1982), 694–700.
51. Stefan, Y., Grasso, S., Perrelet, A., Orci, L., A quantitative immunofluorescent study of the endocrine cell populations in the developing human pancreas. Diabetes 32 (1983), 293–301.
52. Sugiyama, T., Rodriguez, R.T., McLean, G.W., Kim, S.K., Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS. Proc. Natl. Acad. Sci. USA 104 (2007), 175–180.
53. Sullivan, B.A., Hollister-Lock, J., Bonner-Weir, S., Weir, G.C., Reduced Ki67 Staining in the Postmortem State Calls Into Question Past Conclusions About the Lack of Turnover of Adult Human β-Cells. Diabetes 64 (2015), 1698–1702.
54. Tang, L.H., Gonen, M., Hedvat, C., Modlin, I.M., Klimstra, D.S., Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: a comparison of digital image analysis with manual methods. Am. J. Surg. Pathol. 36 (2012), 1761–1770.
55. Thorel, F., Népote, V., Avril, I., Kohno, K., Desgraz, R., Chera, S., Herrera, P.L., Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464 (2010), 1149–1154.
56. Trzpis, M., McLaughlin, P.M., de Leij, L.M., Harmsen, M.C., Epithelial cell adhesion molecule: more than a carcinoma marker and adhesion molecule. Am. J. Pathol. 171 (2007), 386–395.
57. Van Schravendijk, C.F., Kiekens, R., Pipeleers, D.G., Pancreatic beta cell heterogeneity in glucose-induced insulin secretion. J. Biol. Chem. 267 (1992), 21344–21348.
58. Wang, Y.J., McAllister, F., Bailey, J.M., Scott, S.G., Hendley, A.M., Leach, S.D., Ghosh, B., Dicer is required for maintenance of adult pancreatic acinar cell identity and plays a role in Kras-driven pancreatic neoplasia. PLoS ONE, 9, 2014, e113127.
59. Wang, P., Alvarez-Perez, J.C., Felsenfeld, D.P., Liu, H., Sivendran, S., Bender, A., Kumar, A., Sanchez, R., Scott, D.K., Garcia-Ocaña, A., Stewart, A.F., A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nat. Med. 21 (2015), 383–388.
60. Wang, P., Fiaschi-Taesch, N.M., Vasavada, R.C., Scott, D.K., García-Ocaña, A., Stewart, A.F., Diabetes mellitus–advances and challenges in human β-cell proliferation. Nat. Rev. Endocrinol. 11 (2015), 201–212.
61. 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, db160405.
62. Yang, Y.P., Thorel, F., Boyer, D.F., Herrera, P.L., Wright, C.V., Context-specific α- to-β-cell reprogramming by forced Pdx1 expression. Genes Dev. 25 (2011), 1680–1685.
63. Ye, L., Robertson, M.A., Hesselson, D., Stainier, D.Y., Anderson, R.M., Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis. Development 142 (2015), 1407–1417.
64. Yu, K.R., Yang, S.R., Jung, J.W., Kim, H., Ko, K., Han, D.W., Park, S.B., Choi, S.W., Kang, S.K., Schöler, H., Kang, K.S., CD49f enhances multipotency and maintains stemness through the direct regulation of OCT4 and SOX2. Stem Cells 30 (2012), 876–887.