The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes
Open accessAbstract
The interaction between the immune system and endocrine cells in the pancreas is crucial for the initiation and progression of type 1 diabetes (T1D). Imaging mass cytometry (IMC) enables multiplexed assessment of the abundance and localization of more than 30 proteins on the same tissue section at 1-μm resolution. Herein, we have developed a panel of 33 antibodies that allows for the quantification of key cell types including pancreatic exocrine cells, islet cells, immune cells, and stromal components. We employed this panel to analyze 12 pancreata obtained from donors with clinically diagnosed T1D and 6 pancreata from non-diabetic controls. In the pancreata from donors with T1D, we simultaneously visualized significant alterations in islet architecture, endocrine cell composition, and immune cell presentation. Indeed, we demonstrate the utility of IMC to investigate complex events on the cellular level that will provide new insights on the pathophysiology of T1D.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
lmerTest Package: Tests in Linear Mixed Effects Models
Kuznetsova, A., Brockhoff, P. B., & Christensen, R. H. B. (2017) · Journal of Statistical Software · doi:10.18637/jss.v082.i13 · Cited by 24,346
Diagnosis and Classification of Diabetes Mellitus
American Diabetes Association (2010) · Diabetes Care · doi:10.2337/dc11-s062 · Cited by 14,094
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Carpenter, A. E., Jones, T. R., Lamprecht, M. R., Clarke, C., Kang, I. H., Friman, O., Guertin, D. A., Chang, J. H., Lindquist, R. A., Moffat, J., et al. (2006) · Genome biology · doi:10.1186/gb-2006-7-10-r100 · Cited by 5,212
Diagnosis and Classification of diabetes mellitus
Rossi, G. (2014) · Diapedia.org eBooks · doi:10.14496/dia..20 · Cited by 3,212
Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60591-7 · Cited by 2,931
Self-citationmclust 5: Clustering, Classification and Density Estimation Using Gaussian Finite Mixture Models
Scrucca, L., Fop, M., Murphy, T. B., & Adrian, E. R. (2016) · The R Journal · doi:10.32614/rj-2016-021 · Cited by 2,914
Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry
Giesen, C., Wang, H. A. O., Schapiro, D., Zivanovic, N., Jacobs, A., Hattendorf, B., Schüffler, P. J., Grolimund, D., Buhmann, J. M., Brandt, S., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2869 · Cited by 1,951
Eisenbarth (1986) · doi:10.1056/nejm198605223142106 · Cited by 1,659
Gu, G., Dubauskaite, J., & Melton, D. A. (2002) · Development · doi:10.1242/dev.129.10.2447 · Cited by 1,518
A flexible R package for nonnegative matrix factorization
Gaujoux, R., & Seoighe, C. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-367 · Cited by 1,516
Deep profiling of mouse splenic architecture with CODEX multiplexed imaging
Goltsev, Y., Samusik, N., Kennedy-Darling, J., Bhate, S., Hale, M., Vazquez, G., Black, S., & Nolan, G. P. (2018) · Cell · doi:10.1016/j.cell.2018.07.010 · Cited by 1,501 · cited 1×
“During the revision of the manuscript, two additional multiplexed image systems were reported (Goltsev et al., 2018; Gut et al., 2018).”
BackgroundType 1 diabetes: new perspectives on disease pathogenesis and treatment
Atkinson, M. A., & Eisenbarth, G. S. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05415-0 · Cited by 1,491
Self-citationConversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
Thorel, F., Népote, V., Avril, I., Kohno, K., Desgraz, R., Chera, S., & Herrera, P. L. (2010) · Nature · doi:10.1038/nature08894 · Cited by 1,136
Multiplexed ion beam imaging of human breast tumors
Angelo, M., Bendall, S. C., Finck, R., Hale, M. B., Hitzman, C., Borowsky, A. D., Levenson, R. M., Lowe, J. B., Liu, S. D., Zhao, S., et al. (2014) · Nature Medicine · doi:10.1038/nm.3488 · Cited by 1,108
Bottazzo, G. F., Dean, B. M., McNally, J. M., MacKay, E. H., Swift, P. G. F., & Gamble, D. R. (1985) · New England Journal of Medicine · doi:10.1056/nejm198508083130604 · Cited by 932
Analysis of islet inflammation in human type 1 diabetes
Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2009) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2008.03860.x · Cited by 712
Gerich, J. E., Langlois, M., Noacco, C., Karam, J. H., & Forsham, P. H. (1973) · Science · doi:10.1126/science.182.4108.171 · Cited by 688
RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes
Xin, Y., Kim, J., Okamoto, H., Ni, M., Wei, Y., Adler, C., Murphy, A. J., Yancopoulos, G. D., Lin, C., & Gromada, J. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.018 · Cited by 684
Coppieters, K. T., Dotta, F., Amirian, N., Campbell, P. D., Kay, T. W. H., Atkinson, M. A., Roep, B. O., & von Herrath, M. G. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20111187 · Cited by 672
Self-citationhistoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data
Schapiro, D., Jackson, H. W., Raghuraman, S., Fischer, J. R., Zanotelli, V. R., Schulz, D., Giesen, C., Catena, R., Varga, Z., & Bodenmiller, B. (2017) · Nature Methods · doi:10.1038/nmeth.4391 · Cited by 661
Multiplexed protein maps link subcellular organization to cellular states
Gut, G., Herrmann, M. D., & Pelkmans, L. (2018) · Science · doi:10.1126/science.aar7042 · Cited by 510
New Perspectives on the Microvasculature of the Islets of Langerhans in the Rat
Bonner‐Weir, S., & Orci, L. (1982) · Diabetes · doi:10.2337/diab.31.10.883 · Cited by 482
Epigenomic plasticity enables human pancreatic α to β cell reprogramming
Bramswig, N. C., Everett, L. J., Schug, J., Dorrell, C., Liu, C., Luo, Y., Streeter, P. R., Naji, A., Grompe, M., & Kaestner, K. H. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66514 · Cited by 416
Self-citationItoh, N., Hanafusa, T., Miyazaki, A., Miyagawa, J.-I., Yamagata, K., Yamamoto, K., Waguri, M., Imagawa, A., Tamura, S., & Inada, M. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116835 · Cited by 347
Chang, Q., Ornatsky, O., Siddiqui, I. F. S., Loboda, A., Baranov, V. I., & Hedley, D. W. (2017) · Cytometry Part A · doi:10.1002/cyto.a.23053 · Cited by 319
The pathogenesis and natural history of type 1 diabetes.Preprint
Atkinson, M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a007641 · Cited by 316
Self-citationPihoker, C., Gilliam, L. K., Hampe, C. S., & Lernmark, Å. (2005) · Diabetes · doi:10.2337/diabetes.54.suppl_2.s52 · Cited by 314
A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
Damond, N., Engler, S., Zanotelli, V. R., Schapiro, D., Wasserfall, C. H., Kusmartseva, I., Nick, H. S., Thorel, F., Herrera, P. L., Atkinson, M. A., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.11.014 · Cited by 301
Self-citationSchaffer, A., Taylor, B., Benthuysen, J., Liu, J., Thorel, F., Yuan, W., Jiao, Y., Kaestner, K., Herrera, P., Magnuson, M., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003274 · Cited by 246
Self-citationCampbell‐Thompson, M., Wasserfall, C., Kaddis, J., Albanese‐O'Neill, A., Staeva, T., Nierras, C., Moraski, J., Rowe, P., Gianani, R., Eisenbarth, G., et al. (2012) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2316 · Cited by 236
Self-citationVirgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets
van der Meulen, T., Mawla, A. M., DiGruccio, M. R., Adams, M. W., Nies, V. J. M., Dólleman, S., Liu, S., Ackermann, A. M., Cáceres, E. L., Hunter, A. E., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.017 · Cited by 231
Self-citationWang, X., Misawa, R., Zielinski, M. C., Cowen, P., Jo, J., Periwal, V., Ricordi, C., Khan, A., Szust, J., Shen, J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067454 · Cited by 218
Blood flow to the rabbit pancreas with special reference to the islets of langerhans
Lifson, N., Kramlinger, K. G., Mayrand, R. R., & Lender, E. J. (1980) · Gastroenterology · doi:10.1016/0016-5085(80)90371-6 · Cited by 212
α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes
Briššová, M., Haliyur, R., Saunders, D. C., Shrestha, S., Dai, C., Blodgett, D. M., Bottino, R., Campbell‐Thompson, M., Aramandla, R., Poffenberger, G., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.032 · Cited by 211
Self-citationThe diagnosis of insulitis in human type 1 diabetes
Campbell‐Thompson, M., Atkinson, M. A., Butler, A. E., Chapman, N. M., Frisk, G., Gianani, R., Giepmans, B. N. G., von Herrath, M. G., Hyöty, H., Kay, T. W. H., et al. (2013) · Diabetologia · doi:10.1007/s00125-013-3043-5 · Cited by 198
Self-citationLoss of β-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits
Spijker, H. S., Song, H., Ellenbroek, J. H., Roefs, M. M., Engelse, M. A., Bos, E., Koster, A. J., Rabelink, T. J., HANSEN, B. C., Clark, A., et al. (2015) · Diabetes · doi:10.2337/db14-1752 · Cited by 175
Identification of a lobe in the adult human pancreas rich in pancreatic polypeptide
MALAISSE-LAGAE, F., Stefan, Y., Cox, J., Perrelet, A., & Orci, L. (1979) · Diabetologia · doi:10.1007/bf01236270 · Cited by 161
Korpos, É., Kadri, N., Kappelhoff, R., Wegner, J., Overall, C. M., Weber, E., Holmberg, D., Cardell, S., & Sorokin, L. M. (2012) · Diabetes · doi:10.2337/db12-0432 · Cited by 161
Single-Cell Mass Cytometry Analysis of the Human Endocrine Pancreas
Wang, Y. J., Golson, M. L., Schug, J., Traum, D., Liu, C., Vivek, K., Dorrell, C., Naji, A., Powers, A. C., Chang, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.007 · Cited by 157
Self-citationExtracellular Matrix Components in the Pathogenesis of Type 1 Diabetes
Bogdani, M., Korpos, É., Simeonovic, C. J., Parish, C. R., Sorokin, L. M., & Wight, T. N. (2014) · Current Diabetes Reports · doi:10.1007/s11892-014-0552-7 · Cited by 129
GABA and Artesunate Do Not Induce Pancreatic α-to-β Cell Transdifferentiation In Vivo
Ackermann, A. M., Moss, N., & Kaestner, K. H. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.07.002 · Cited by 115
Self-citationPhillips, J. M., Parish, N. M., Bland, C., Sawyer, Y., Peña, H. D. L., & Cooke, A. (2009) · The Review of Diabetic Studies · doi:10.1900/rds.2009.6.97 · Cited by 113
Wang, G., Rajpurohit, S. K., Delaspre, F., Walker, S. L., White, D. T., Ceasrine, A. M., Kuruvilla, R., Li, R., Shim, J. S., Liu, J. O., et al. (2015) · eLife · doi:10.7554/elife.08261 · Cited by 96
Severe acute pancreatitis after percutaneous biopsy of the pancreas
Mueller, P. R., Miketic, L. M., Simeone, J. F., Silverman, S., Saini, S., WITTENBERG, J., Pf, H., Steiner, E., & Bh, F. (1988) · American Journal of Roentgenology · doi:10.2214/ajr.151.3.493 · Cited by 88
The central role of antigen presentation in islets of Langerhans in autoimmune diabetes
Calderón, B., Carrero, J. A., & Unanue, E. R. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.10.011 · Cited by 49
Beta-cell destruction and preservation in childhood and adult onset type 1 diabetes
Poudel, A., Savari, O., Striegel, D. A., Periwal, V., Taxy, J. B., Millis, J. M., Witkowski, P., Atkinson, M. A., & Hara, M. (2015) · Endocrine · doi:10.1007/s12020-015-0534-9 · Cited by 45
Self-citationStefan, Y., GRASSO, S. G., Perrelet, A., & Orci, L. (1982) · Diabetologia · doi:10.1007/bf01271177 · Cited by 39
Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora’s box
Atkinson, M. A. (2014) · Diabetologia · doi:10.1007/s00125-013-3159-7 · Cited by 35
Self-citationAsadi, A., Bruin, J. E., & Kieffer, T. J. (2015) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155415576541 · Cited by 34
Cited by
Sorted by citations
Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?)
Roep, B. O., Thomaidou, S., van Tienhoven, R., & Zaldumbide, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00443-4 · Cited by 675
Taylor, M. J., Lukowski, J. K., & Anderton, C. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.0c00439 · Cited by 306
A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry
Damond, N., Engler, S., Zanotelli, V. R., Schapiro, D., Wasserfall, C. H., Kusmartseva, I., Nick, H. S., Thorel, F., Herrera, P. L., Atkinson, M. A., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.11.014 · Cited by 301
Self-citationFasolino, M., Schwartz, G. W., Patil, A. R., Mongia, A., Golson, M. L., Wang, Y. J., Morgan, A. R., Liu, C., Schug, J., Liu, J., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00531-x · Cited by 225
Self-citationImmune monitoring using mass cytometry and related high-dimensional imaging approaches
Hartmann, F. J., & Bendall, S. C. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0338-z · Cited by 208
Metadata
- Authors
- Wang, Y. J., Traum, D., Schug, J., Gao, L., Liu, C., Atkinson, M. A., Powers, A. C., Feldman, M. D., Naji, A., Chang, K.-M., & Kaestner, K. H.
- Affiliations
- University of Pennsylvania (US)
- Philadelphia VA Medical Center (US)
- University of Florida Health (US)
- VA Tennessee Valley Healthcare System (US)
- Corresponding author
- Kaestner, Klaus H.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 29
- Issue
- 3
- Pages
- 769-783.e4
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6436557
- OpenAlex
- W2913147009
- Cited by
- 228
- References
- 51
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 28 · 2023: 22 · 2022: 32 · 2021: 47 · 2020: 26 · 2019: 20
- FWCI
- 18.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIDDK (UC4 DK112217, UC4 DK112232, UC4 DK108132, UC4 DK104119)
- University of Pennsylvania Diabetes Research Center (P30 DK19525)
- Vanderbilt Diabetes Research and Training Center (P30 DK20593)
- Department of Veterans Affairs
- JDRF
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes, imaging mass cytometry, pancreatic islets, endocrine pancreas, immune cells, islet architecture, pancreatic stroma, exocrine pancreas, endocrine-immune interaction
- MeSH terms
- Diabetes Mellitus, Type 1, Humans, Immune System, Islets of Langerhans, Image Cytometry, Endocrine Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
