کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3001587 1180651 2016 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes
ترجمه فارسی عنوان
ادغام ATAC-seq و RNA-seq ژن های امضاي سلول های آلفا و بتا انسان را شناسایی می کند
کلمات کلیدی
جزیره؛ سلول آلفا؛ سلول بتا؛ دیابت؛ Epigenetics؛ تست کروماتین ATAC-sec، تست کروماتین قابل دسترس با ترانسپازا با توالی انتخابی بالا؛ FAIRE-seq، جداسازی فرمالدئید از عناصر تنظیم کننده و دنباله های بالا
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های درون ریز و اتونومیک
چکیده انگلیسی


• Defined open chromatin regions in sorted human α- and β-cells using ATAC-seq.
• Detected type 2 diabetes-associated risk loci in human α- and β-cell open chromatin.
• Classified human α- and β-cell-specific transcripts using mRNA-seq.
• Discovered novel human α- and β-cell signature proteins.
• Identified potential gene regulatory regions by integrating ATAC- and mRNA-seq data.

ObjectiveAlthough glucagon-secreting α-cells and insulin-secreting β-cells have opposing functions in regulating plasma glucose levels, the two cell types share a common developmental origin and exhibit overlapping transcriptomes and epigenomes. Notably, destruction of β-cells can stimulate repopulation via transdifferentiation of α-cells, at least in mice, suggesting plasticity between these cell fates. Furthermore, dysfunction of both α- and β-cells contributes to the pathophysiology of type 1 and type 2 diabetes, and β-cell de-differentiation has been proposed to contribute to type 2 diabetes. Our objective was to delineate the molecular properties that maintain islet cell type specification yet allow for cellular plasticity. We hypothesized that correlating cell type-specific transcriptomes with an atlas of open chromatin will identify novel genes and transcriptional regulatory elements such as enhancers involved in α- and β-cell specification and plasticity.MethodsWe sorted human α- and β-cells and performed the “Assay for Transposase-Accessible Chromatin with high throughput sequencing” (ATAC-seq) and mRNA-seq, followed by integrative analysis to identify cell type-selective gene regulatory regions.ResultsWe identified numerous transcripts with either α-cell- or β-cell-selective expression and discovered the cell type-selective open chromatin regions that correlate with these gene activation patterns. We confirmed cell type-selective expression on the protein level for two of the top hits from our screen. The “group specific protein” (GC; or vitamin D binding protein) was restricted to α-cells, while CHODL (chondrolectin) immunoreactivity was only present in β-cells. Furthermore, α-cell- and β-cell-selective ATAC-seq peaks were identified to overlap with known binding sites for islet transcription factors, as well as with single nucleotide polymorphisms (SNPs) previously identified as risk loci for type 2 diabetes.ConclusionsWe have determined the genetic landscape of human α- and β-cells based on chromatin accessibility and transcript levels, which allowed for detection of novel α- and β-cell signature genes not previously known to be expressed in islets. Using fine-mapping of open chromatin, we have identified thousands of potential cis-regulatory elements that operate in an endocrine cell type-specific fashion.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Metabolism - Volume 5, Issue 3, March 2016, Pages 233–244
نویسندگان
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