Alpha TC1 and Beta-TC-6 genomic profiling uncovers both shared and distinct transcriptional regulatory features with their primary islet counterparts.
Alpha TC1 and Beta-TC-6 genomic profiling uncovers both shared and distinct transcriptional regulatory features with their primary islet counterparts.
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DOI：
10.1038/s41598-017-12335-1
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发表时间：
2017-09-20
影响因子：
4.6
通讯作者：
Stitzel ML
中科院分区：
文献类型：
--
作者：
Lawlor N;Youn A;Kursawe R;Ucar D;Stitzel ML
α TC 1（α TC 1）和β-TC-6（β TC 6）小鼠胰岛细胞系是胰岛（dys）功能和2型糖尿病（T2 D）的细胞模型。然而，这些细胞的基因组特征及其与原代胰岛α和β细胞的相似性尚不明确。在这里，我们报告了α TC 1和β TC 6细胞的表观基因组（ATAC-seq）和转录组（RNA-seq）景观。每种细胞类型表现出其原代胰岛细胞对应物的特征，包括β（例如，Pdx 1）和alpha（例如，Arx）细胞转录因子（TF），并在α TC 1/β TC 6顺式调控元件中富集这些TF的结合基序。α TC 1/β TC 6转录组与原代小鼠/人α和β细胞的转录组显著重叠。我们的数据进一步表明，ATAC-seq检测细胞类型的细胞特异性调控元件，所述细胞类型包含≥ 20%的混合细胞群体。我们在人类胰岛中的33个基因座中鉴定了α TC 1/β TC 6顺式调节元件，这些元件与含有2型糖尿病（T2 D）相关SNP的元件正交，表明这些细胞可用于分析这些区域中的T2 D分子遗传学。总之，这些图谱为α TC 1/β TC 6和原代胰岛细胞之间的保守调控结构提供了重要的见解，这些结构可以在功能（表观）基因组方法中利用，以剖析控制胰岛细胞身份和功能的遗传和分子因素。
Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) mouse islet cell lines are cellular models of islet (dys)function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of αTC1 and βTC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in αTC1/βTC6 cis-regulatory elements. αTC1/βTC6 transcriptomes overlap significantly with the transcriptomes of primary mouse/human alpha and beta cells. Our data further indicate that ATAC-seq detects cell-specific regulatory elements for cell types comprising ≥ 20% of a mixed cell population. We identified αTC1/βTC6 cis-regulatory elements orthologous to those containing type 2 diabetes (T2D)-associated SNPs in human islets for 33 loci, suggesting these cells’ utility to dissect T2D molecular genetics in these regions. Together, these maps provide important insights into the conserved regulatory architecture between αTC1/βTC6 and primary islet cells that can be leveraged in functional (epi)genomic approaches to dissect the genetic and molecular factors controlling islet cell identity and function.
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影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
30.8
作者：
Dooley J;Tian L;Schonefeldt S;Delghingaro-Augusto V;Garcia-Perez JE;Pasciuto E;Di Marino D;Carr EJ;Oskolkov N;Lyssenko V;Franckaert D;Lagou V;Overbergh L;Vandenbussche J;Allemeersch J;Chabot-Roy G;Dahlstrom JE;Laybutt DR;Petrovsky N;Socha L;Gevaert K;Jetten AM;Lambrechts D;Linterman MA;Goodnow CC;Nolan CJ;Lesage S;Schlenner SM;Liston A
通讯作者：
Liston A
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A
影响因子：
1.5
作者：
Choi, SE;Choi, KM;Park, CG
通讯作者：
Park, CG
影响因子：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.