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10.1016/j.molmet.2016.01.002 http://scihub22266oqcxt.onion/10.1016/j.molmet.2016.01.002 C4770267!4770267!26977395     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Metab 2016 ; 5 (3): 233-44 Nephropedia Template TP {{tp|p=26977395|t=2016. Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes |pdf=|usr=}}{{26977395}} gab.com Text Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes JO: Mol Metab http://www.kidney.de/pget.php?&tw=1&pmid=26977395 #FOAvip Objective: Although glucagon-secreting ?-cells and insulin-secreting ?-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 ?-cells can stimulate repopulation via transdifferentiation of ?-cells, at least in mice, suggesting plasticity between these cell fates. Furthermore, dysfunction of both ?- and ?-cells contributes to the pathophysiology of type 1 and type 2 diabetes, and ?-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 ?- and ?-cell specification and plasticity. Methods: We sorted human ?- and ?-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. Results: We identified numerous transcripts with either ?-cell- or ?-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 ?-cells, while CHODL (chondrolectin) immunoreactivity was only present in ?-cells. Furthermore, ?-cell- and ?-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. Conclusions: We have determined the genetic landscape of human ?- and ?-cells based on chromatin accessibility and transcript levels, which allowed for detection of novel ?- and ?-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. Twit Text FOAVip Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes ????Mol Metab http://www.kidney.de/pget.php?&tw=1&pmid=26977395 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26977395 #FOAvip English Wikipedia <ref>{{Cite pmid|26977395}}</ref> Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes #MMPMID26977395 Ackermann AM; Wang Z; Schug J; Naji A; Kaestner KH Mol Metab 2016[Mar]; 5 (3): 233-44 PMID26977395show ga Objective: Although glucagon-secreting ?-cells and insulin-secreting ?-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 ?-cells can stimulate repopulation via transdifferentiation of ?-cells, at least in mice, suggesting plasticity between these cell fates. Furthermore, dysfunction of both ?- and ?-cells contributes to the pathophysiology of type 1 and type 2 diabetes, and ?-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 ?- and ?-cell specification and plasticity. Methods: We sorted human ?- and ?-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. Results: We identified numerous transcripts with either ?-cell- or ?-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 ?-cells, while CHODL (chondrolectin) immunoreactivity was only present in ?-cells. Furthermore, ?-cell- and ?-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. Conclusions: We have determined the genetic landscape of human ?- and ?-cells based on chromatin accessibility and transcript levels, which allowed for detection of novel ?- and ?-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. äIntegration of ATAC-seq and RNA-seq identifies human alpha cell and be(epmc).pdf DeepDyve Pubget Overpricing