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| Status |
Public on Nov 09, 2016 |
| Title |
Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes [bulk] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Blood glucose levels are tightly controlled by the coordinated action of at least five cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 diabetes (T2D). Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet dysfunction, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single cell transcriptomes for 617 islet cells after profiling ~1000 cells from non-diabetic (ND) and T2D human organ donors. Analyses of non-diabetic single cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell type-specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis.
Grant ID: Award No. W81XWH-16-1-0130
Grant title: Peer Reviewed Medical Research Program
Funding Source: Assistant Secretary of Defense for Health Affairs
Affiliation: Jackson Laboratory for Genomic Medicine, Farmington, CT
Name: Michael Stitzel
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| Overall design |
RNA-seq profiles of 24 human pancreatic islet/other bulk cell samples obtained from non-diabetic and type 2 diabetic cadaveric organ donors.
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| Contributor(s) |
Lawlor N, George J, Bolisetty M, Kursawe R, Sun L, Sivakamasundari V, Kycia I, Robson P, Stitzel ML |
| Citation(s) |
27864352 |
| BioProject |
PRJNA323853 |
| Submission date |
Sep 06, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Michael Stitzel |
| E-mail(s) |
Michael.Stitzel@jax.org
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| Organization name |
The Jackson Laboratory
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| Street address |
10 Discovery Drive
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| City |
Farmington |
| State/province |
CT |
| ZIP/Postal code |
06032 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE86473 |
Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE86468_GEO.bulk.islet.processed.data.RSEM.raw.expected.counts.csv.gz |
1.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data provided as supplementary file |
| Processed data are available on Series record |
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