Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes.
Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes.
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DOI：
10.1016/j.cmet.2016.08.020
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发表时间：
2016-10-11
期刊：
影响因子：
29
通讯作者：
Sandberg R
中科院分区：
文献类型：
--
作者：
Segerstolpe Å;Palasantza A;Eliasson P;Andersson EM;Andréasson AC;Sun X;Picelli S;Sabirsh A;Clausen M;Bjursell MK;Smith DM;Kasper M;Ämmälä C;Sandberg R
胰岛内的激素分泌细胞在代谢稳态和疾病中起重要作用。然而，它们的转录特征仍然是不完整的。在这里，我们对来自健康和2型糖尿病供体的数千个人类胰岛细胞的转录组进行了测序。我们可以为每种内分泌和外分泌细胞类型定义特定的遗传程序，甚至为罕见的δ，γ，ε和星状细胞，并揭示α，β和腺泡细胞的亚群。有趣的是，δ细胞表达了几种重要的受体，表明这些细胞在整合旁分泌和全身代谢信号方面的重要性尚未被认识。先前与肥胖或糖尿病相关的基因被发现与BMI相关。最后，以细胞类型分辨的方式比较健康和T2D转录组发现了未来功能研究的候选者。总之，我们的分析证明了所产生的单细胞基因表达资源的实用性。在内分泌和外分泌细胞类型中鉴定了亚群，与肥胖或糖尿病相关的基因具有与BMI相关的表达，在2型糖尿病个体中发现了转录改变。使用单细胞转录组学生成健康和2型糖尿病供体的单个胰腺内分泌和外分泌细胞的转录谱。他们揭示了细胞类型特异性基因表达和新的亚群，以及与BMI和糖尿病基因表达改变的基因相关性。
Hormone-secreting cells within pancreatic islets of Langerhans play important roles in metabolic homeostasis and disease. However, their transcriptional characterization is still incomplete. Here, we sequenced the transcriptomes of thousands of human islet cells from healthy and type 2 diabetic donors. We could define specific genetic programs for each individual endocrine and exocrine cell type, even for rare δ, γ, ε, and stellate cells, and revealed subpopulations of α, β, and acinar cells. Intriguingly, δ cells expressed several important receptors, indicating an unrecognized importance of these cells in integrating paracrine and systemic metabolic signals. Genes previously associated with obesity or diabetes were found to correlate with BMI. Finally, comparing healthy and T2D transcriptomes in a cell-type resolved manner uncovered candidates for future functional studies. Altogether, our analyses demonstrate the utility of the generated single-cell gene expression resource. Single-cell RNA-seq enabled molecular profiling of rare human pancreatic cells Subpopulations were identified within endocrine and exocrine cell types Genes associated with obesity or diabetes had correlating expression with BMI Transcriptional alterations found in type 2 diabetic individuals Segerstolpe et al. use single-cell transcriptomics to generate transcriptional profiles of individual pancreatic endocrine and exocrine cells of healthy and type 2 diabetic donors. They revealed cell-type-specific gene expression and novel subpopulations, as well as gene correlations to BMI and gene expression alterations in diabetes.
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DOI：
10.1016/b978-0-12-800101-1.00002-8
发表时间：
2014
影响因子：
--
作者：
Nadkarni, Prashant;Chepurny, Oleg G.;Holz, George G.
通讯作者：
Holz, George G.
影响因子：
29
作者：
Kloeting, Nora;Graham, Timothy E.;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
7.7
作者：
Kieffer, TJ;Keller, RS;Habener, JF
通讯作者：
Habener, JF
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
影响因子：
7
作者：
Nica AC;Ongen H;Irminger JC;Bosco D;Berney T;Antonarakis SE;Halban PA;Dermitzakis ET
通讯作者：
Dermitzakis ET