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| Status |
Public on Jan 19, 2023 |
| Title |
Chromatin accessibility differences between alpha, beta, and delta cells identifies common and cell type-specific enhancers |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
High throughput sequencing has enabled the interrogation of the transcriptomic landscape of glucagon-secreting alpha cells, insulin-secreting beta cells, and somatostatin-secreting delta cells. These approaches have furthered our understanding of expression patterns that define healthy or diseased islet cell types and helped explicate some of the intricacies between major islet cell crosstalk and glucose regulation. All three endocrine cell types derive from a common pancreatic progenitor, yet alpha and beta cells have partially opposing functions, and delta cells modulate and control insulin and glucagon release. While gene signatures that define and maintain cellular identity have been widely explored, the underlying epigenetic components are incompletely characterized and understood. Chromatin accessibility and remodeling is a dynamic attribute that plays a critical role to determine and maintain cellular identity. Here, we compare and contrast the chromatin landscape between mouse alpha, beta, and delta cells using ATAC-Seq to evaluate the significant differences in chromatin accessibility. The similarities and differences in chromatin accessibility between these related islet endocrine cells help define their fate in support of their distinct functional roles. We identify patterns that suggest that both alpha and delta cells are poised, but repressed, from becoming beta-like. We also identify patterns in differentially enriched chromatin that have transcription factor motifs preferentially associated with different regions of the genome. Finally, we identify and visualize both novel and previously discovered common endocrine- and cell specific- enhancer regions across differentially enriched chromatin.
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| Overall design |
mIns1-H2b-mCherry [1] x Rosa-LSL-YFP crossed to either Sst-Cre [44] or Gcg-Cre [45] triple transgenic mice were pooled by sex, each sample yielding a median of 20,000 cells, with islet isolation and FACS-sorting as previously described (Supplemental Fig. 1) [1, 46-48]. A minimum of two replicates were used in all analyses.
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| Contributor(s) |
Mawla AM, van der Meulen T, Huising MO |
| Citation(s) |
37069576 |
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| Submission date |
Sep 22, 2022 |
| Last update date |
Apr 18, 2023 |
| Contact name |
Mark O. Huising |
| E-mail(s) |
mhuising@ucdavis.edu
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| Organization name |
University of California, Davis
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| Department |
Neurobiology, Physiology and Behavior
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| Lab |
Huising Lab
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| Street address |
One Shields Ave
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| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95616 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA883384 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213970_RAW.tar |
3.1 Gb |
(http)(custom) |
TAR (of BAM, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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