Pseudotime ordering of single human B-cells reveals states of insulin production and unfolded protein response

Diabetes

Volumn 67, Issue 9, 2018, Pages 1783-1794

  Xin, Yurong ^a   Gutierrez, Giselle Dominguez ^a   Okamoto, Haruka ^a   Kim, Jinrang ^a   Lee, Ann Hwee ^a   Adler, Christina ^a   Ni, Min ^a   Yancopoulos, George D ^a   Murphy, Andrew J ^a   Gromada, Jesper ^a  

^a REGENERON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; HEMOGLOBIN A1C; INSULIN; BIOLOGICAL MARKER; MESSENGER RNA; PROINSULIN; TRANSCRIPTION FACTOR;

ANIMAL CELL; APOPTOSIS; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE SUBPOPULATION; CELL DEDIFFERENTIATION; CELL PROLIFERATION; CELL STRESS; ENDOPLASMIC RETICULUM STRESS; ENERGY YIELD; FLUORESCENCE IN SITU HYBRIDIZATION; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; INSULIN SYNTHESIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; RNA SEQUENCE; STEM CELL SELF-RENEWAL; UNFOLDED PROTEIN RESPONSE; CELL CULTURE; CHEMISTRY; CYTOLOGY; DNA MICROARRAY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETIC DATABASE; GENETICS; KINETICS; METABOLISM; MULTIGENE FAMILY; NUCLEIC ACID ANALYSIS; PANCREAS ISLET BETA CELL; PRINCIPAL COMPONENT ANALYSIS; SECRETION (PROCESS); SEQUENCE ANALYSIS; SINGLE CELL ANALYSIS;

BIOMARKERS; CELL PROLIFERATION; CELLS, CULTURED; DATABASES, GENETIC; ENDOPLASMIC RETICULUM STRESS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; INSULIN; INSULIN-SECRETING CELLS; KINETICS; MULTIGENE FAMILY; NUCLEOTIDE MAPPING; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PRINCIPAL COMPONENT ANALYSIS; PROINSULIN; RNA, MESSENGER; SEQUENCE ANALYSIS, RNA; SINGLE-CELL ANALYSIS; TRANSCRIPTION FACTORS; UNFOLDED PROTEIN RESPONSE;

EID: 85052700858     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db18-0365     Document Type: Article

References (58)

1. Scheuner D, Kaufman RJ. The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes. Endocr Rev 2008;29:317-333
2. Schuit FC, In't Veld PA, Pipeleers DG. Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells. Proc Natl Acad Sci U S A 1988;85:3865-3869
3. Liu M, Haataja L, Wright J, et al. Mutant INS-gene induced diabetes of youth: proinsulin cysteine residues impose dominant-negative inhibition on wild-type proinsulin transport. PLoS One 2010;5:e13333
4. Liu M, Li Y, Cavener D, Arvan P. Proinsulin disulfide maturation and misfolding in the endoplasmic reticulum. J Biol Chem 2005;280:13209-13212
5. Wang J, Chen Y, Yuan Q, Tang W, Zhang X, Osei K. Control of precursor maturation and disposal is an early regulative mechanism in the normal insulin production of pancreatic b-cells. PLoS One 2011;6:e19446
6. Wang J, Osei K. Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in b-cells. Biochem Biophys Res Commun 2011; 411:150-155
7. Eizirik DL, Cardozo AK, Cnop M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev 2008;29:42-61
8. Papa FR. Endoplasmic reticulum stress, pancreatic b-cell degeneration, and diabetes. Cold Spring Harb Perspect Med 2012;2:a007666
9. Vetere A, Choudhary A, Burns SM, Wagner BK. Targeting the pancreatic b-cell to treat diabetes. Nat Rev Drug Discov 2014;13:278-289
10. Schuit F, De Vos A, Farfari S, et al. Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem 1997;272:18572-18579
11. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 1996;20:463-466
12. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997;46:1733-1742
13. Hasnain SZ, Prins JB, McGuckin MA. Oxidative and endoplasmic reticulum stress in b-cell dysfunction in diabetes. J Mol Endocrinol 2016;56:R33-R54
14. Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic b-cell death. Trends Endocrinol Metab 2011;22:266-274
15. Gutierrez GD, Gromada J, Sussel L. Heterogeneity of the pancreatic beta cell. Front Genet 2017;8:22
16. Xin Y, Kim J, Okamoto H, et al. RNA sequencing of single human islet cells reveals type 2 diabetes genes. Cell Metab 2016;24:608-615
17. Baron M, Veres A, Wolock SL, et al. A single-cell transcriptomic map of the human and mouse pancreas reveals inter- and intra-cell population structure. Cell Syst 2016;3:346-360.e4
18. Segerstolpe Å, Palasantza A, Eliasson P, et al. Single-cell transcriptome profiling of human pancreatic islets in health and type 2 diabetes. Cell Metab 2016;24:593-607
19. Muraro MJ, Dharmadhikari G, Grun D, et al. A single-cell transcriptome atlas of the human pancreas. Cell Syst 2016;3:385-394.e3
20. Dominguez D, Tsai YH, Gomez N, Jha DK, Davis I, Wang Z. A high-resolution transcriptome map of cell cycle reveals novel connections between periodic genes and cancer. Cell Res 2016;26:946-962
21. Liang G, Audas TE, Li Y, et al. Luman/CREB3 induces transcription of the endoplasmic reticulum (ER) stress response protein Herp through an ER stress response element. Mol Cell Biol 2006;26:7999-8010
22. Jiang HY, Wek SA, McGrath BC, et al. Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. Mol Cell Biol 2004;24:1365-1377
23. Ediger BN, Du A, Liu J, et al. Islet-1 is essential for pancreatic b-cell function. Diabetes 2014;63:4206-4217
24. Gao T, McKenna B, Li C, et al. Pdx1 maintains b cell identity and function by repressing an a cell program. Cell Metab 2014;19:259-271
25. Hang Y, Stein R. MafA and MafB activity in pancreatic b cells. Trends Endocrinol Metab 2011;22:364-373
26. Gu C, Stein GH, Pan N, et al. Pancreatic beta cells require NeuroD to achieve and maintain functional maturity. Cell Metab 2010;11:298-310
27. Gutiérrez GD, Bender AS, Cirulli V, et al. Pancreatic b cell identity requires continual repression of non-b cell programs. J Clin Invest 2017;127:244-259
28. Arda HE, Li L, Tsai J, et al. Age-dependent pancreatic gene regulation reveals mechanisms governing human b cell function. Cell Metab 2016;23: 909-920
29. Sloan KE, Bohnsack MT, Watkins NJ. The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress. Cell Rep 2013;5:237-247
30. Nicholas LM, Valtat B, Medina A, et al. Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic b-cells. Mol Metab 2017;6:651-663
31. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 2013;53:401-426
32. Abebe T, Mahadevan J, Bogachus L, et al. Nrf2/antioxidant pathway mediates b cell self-repair after damage by high-fat diet-induced oxidative stress. JCI Insight 2017;2
33. Lipson KL, Fonseca SG, Ishigaki S, et al. Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. Cell Metab 2006;4:245-254
34. Espinosa-Diez C, Miguel V, Mennerich D, et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol 2015;6:183-197
35. Gray JP, Karandrea S, Burgos DZ, Jaiswal AA, Heart EA. NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic b-cells. Toxicol Lett 2016;262:1-11
36. Orino K, Lehman L, Tsuji Y, Ayaki H, Torti SV, Torti FM. Ferritin and the response to oxidative stress. Biochem J 2001;357:241-247
37. Shi H, Bencze KZ, Stemmler TL, Philpott CC. A cytosolic iron chaperone that delivers iron to ferritin. Science 2008;320:1207-1210
38. Clements CM, McNally RS, Conti BJ, Mak TW, Ting JP. DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc Natl Acad Sci U S A 2006;103:15091-15096
39. Jain A, Lamark T, Sjøttem E, et al. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 2010;285:22576-22591
40. Chen W, Sun Z, Wang XJ, et al. Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell 2009;34:663-673
41. Zhang J, Tong W, Sun H, et al. Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3b pathway. Exp Gerontol 2017;100:77-86
42. Bensellam M, Montgomery MK, Luzuriaga J, Chan JY, Laybutt DR. Inhibitor of differentiation proteins protect against oxidative stress by regulating the antioxidant-mitochondrial response in mouse beta cells. Diabetologia 2015;58: 758-770
43. Sharma RB, O'Donnell AC, Stamateris RE, et al. Insulin demand regulates b cell number via the unfolded protein response. J Clin Invest 2015;125:3831-3846
44. Szabat M, Page MM, Panzhinskiy E, et al. Reduced insulin production relieves endoplasmic reticulum stress and induces b cell proliferation. Cell Metab 2016;23:179-193
45. Khalfallah O, Rouleau M, Barbry P, Bardoni B, Lalli E. Dax-1 knockdown in mouse embryonic stem cells induces loss of pluripotency and multilineage differentiation. Stem Cells 2009;27:1529-1537
46. Parker JB, Yin H, Vinckevicius A, Chakravarti D. Host cell factor-1 recruitment to E2F-bound and cell-cycle-control genes is mediated by THAP11 and ZNF143. Cell Rep 2014;9:967-982
47. Murata K, Hattori M, Hirai N, et al. Hes1 directly controls cell proliferation through the transcriptional repression of p27Kip1. Mol Cell Biol 2005;25:4262-4271
48. El Yakoubi W, Borday C, Hamdache J, et al. Hes4 controls proliferative properties of neural stem cells during retinal ontogenesis. Stem Cells 2012;30: 2784-2795
49. Klochendler A, Caspi I, Corem N, et al. The genetic program of pancreatic b-cell replication in vivo. Diabetes 2016;65:2081-2093
50. Riganti C, Gazzano E, Polimeni M, Aldieri E, Ghigo D. The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Radic Biol Med 2012;53:421-436
51. Zhang Z, Liew CW, Handy DE, et al. High glucose inhibits glucose-6phosphate dehydrogenase, leading to increased oxidative stress and beta-cell apoptosis. FASEB J 2010;24:1497-1505
52. Stanton RC. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life 2012;64:362-369
53. Talchai C, Xuan S, Lin HV, Sussel L, Accili D. Pancreatic b cell dedifferentiation as a mechanism of diabetic b cell failure. Cell 2012;150:1223-1234
54. Ichii H, Inverardi L, Pileggi A, et al. A novel method for the assessment of cellular composition and beta-cell viability in human islet preparations. Am J Transplant 2005;5:1635-1645
55. Rorsman P, Renström E. Insulin granule dynamics in pancreatic beta cells. Diabetologia 2003;46:1029-1045
56. Kendall DM, Sutherland DE, Najarian JS, Goetz FC, Robertson RP. Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. N Engl J Med 1990;322:898-903
57. Menge BA, Schrader H, Breuer TG, et al. Metabolic consequences of a 50% partial pancreatectomy in humans. Diabetologia 2009;52:306-317
58. Meier JJ, Bonadonna RC. Role of reduced b-cell mass versus impaired b-cell function in the pathogenesis of type 2 diabetes. Diabetes Care 2013;36(Suppl. 2): S113-S119