Cell-type, allelic, and genetic signatures in the human pancreatic beta cell transcriptome.
Cell-type, allelic, and genetic signatures in the human pancreatic beta cell transcriptome.
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DOI：
10.1101/gr.150706.112
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发表时间：
2013-09
期刊：
影响因子：
7
通讯作者：
Dermitzakis ET
中科院分区：
文献类型：
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作者：
Nica AC;Ongen H;Irminger JC;Bosco D;Berney T;Antonarakis SE;Halban PA;Dermitzakis ET
阐明常见疾病的病理生理和分子特性以及开发有针对性和有效的治疗方法取决于对相关细胞类型和组织的研究。朗格汉斯胰岛内的胰腺β细胞在1型和2型糖尿病的发病机制中起着核心作用。迄今为止，描述人类β细胞的分化状态一直受到技术（低分辨率微阵列）和生物学限制（整个胰岛制备而不是分离的β细胞）的阻碍。我们通过对来自11个个体的纯化β细胞进行深度RNA测序来规避这些问题，在这里提出了人类β细胞转录组的第一个表征。我们首次比较了β细胞、全胰岛和β细胞耗尽胰岛制剂之间的基因表达谱，从而揭示了β细胞特异性表达和剪接特征。此外，我们证明在β细胞中持续增加表达的基因具有神经元样特性，这是先前假设的信号。最后，我们在β细胞中发现了广泛的等位基因表达不平衡的证据，并发现了活跃的遗传调控变异（eQTLs）。人类β细胞的第一个分子蓝图提供了对其分化功能的生物学见解，包括与两种主要糖尿病类型相关的关键基因的表达。
Elucidating the pathophysiology and molecular attributes of common disorders as well as developing targeted and effective treatments hinges on the study of the relevant cell type and tissues. Pancreatic beta cells within the islets of Langerhans are centrally involved in the pathogenesis of both type 1 and type 2 diabetes. Describing the differentiated state of the human beta cell has been hampered so far by technical (low resolution microarrays) and biological limitations (whole islet preparations rather than isolated beta cells). We circumvent these by deep RNA sequencing of purified beta cells from 11 individuals, presenting here the first characterization of the human beta cell transcriptome. We perform the first comparison of gene expression profiles between beta cells, whole islets, and beta cell depleted islet preparations, revealing thus beta-cell–specific expression and splicing signatures. Further, we demonstrate that genes with consistent increased expression in beta cells have neuronal-like properties, a signal previously hypothesized. Finally, we find evidence for extensive allelic imbalance in expression and uncover genetic regulatory variants (eQTLs) active in beta cells. This first molecular blueprint of the human beta cell offers biological insight into its differentiated function, including expression of key genes associated with both major types of diabetes.
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影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
4.4
作者：
Danzer, Carsten;Eckhardt, Katrin;Krek, Wilhelm
通讯作者：
Krek, Wilhelm
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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