Pseudotime Ordering Single-Cell Transcriptomic of β Cells Pancreatic Islets in Health and Type 2 Diabetes.

IF 3.7 Q2 GENETICS & HEREDITY Phenomics (Cham, Switzerland) Pub Date : 2021-10-01 DOI:10.1007/s43657-021-00024-z
Kaixuan Bao, Zhicheng Cui, Hui Wang, Hui Xiao, Ting Li, Xingxing Kong, Tiemin Liu
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引用次数: 4

Abstract

β cells are defined by the ability to produce and secret insulin. Recent studies have evaluated that human pancreatic β cells are heterogeneous and demonstrated the transcript alterations of β cell subpopulation in diabetes. Single-cell RNA sequence (scRNA-seq) analysis helps us to refine the cell types signatures and understand the role of the β cells during metabolic challenges and diseases. Here, we construct the pseudotime trajectory of β cells from publicly available scRNA-seq data in health and type 2 diabetes (T2D) based on highly dispersed and highly expressed genes using Monocle2. We identified three major states including 1) Normal branch, 2) Obesity-like branch and 3) T2D-like branch based on biomarker genes and genes that give rise to bifurcation in the trajectory. β cell function-maintain-related genes, insulin expression-related genes, and T2D-related genes enriched in three branches, respectively. Continuous pseudotime spectrum might suggest that β cells transition among different states. The application of pseudotime analysis is conducted to clarify the different cell states, providing novel insights into the pathology of β cells in T2D.

Supplementary information: The online version contains supplementary material is available at 10.1007/s43657-021-00024-z.

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健康和2型糖尿病患者胰岛β细胞的伪时间顺序单细胞转录组学研究
β细胞的定义是产生和分泌胰岛素的能力。最近的研究已经评估了人类胰腺β细胞是异质的,并证明了β细胞亚群在糖尿病中的转录改变。单细胞RNA序列(scRNA-seq)分析有助于我们完善细胞类型特征,并了解β细胞在代谢挑战和疾病中的作用。在这里,我们使用Monocle2基于高度分散和高表达的基因,从公开可用的健康和2型糖尿病(T2D)患者的scRNA-seq数据构建了β细胞的伪时间轨迹。基于生物标志物基因和导致轨迹分叉的基因,我们确定了三种主要状态,包括1)正常分支,2)肥胖样分支和3)t2d样分支。β细胞功能维持相关基因、胰岛素表达相关基因和t2d相关基因分别富集于三个分支。连续的伪时间谱可能提示β细胞在不同状态间转换。应用伪时间分析来澄清不同的细胞状态,为T2D中β细胞的病理提供新的见解。补充信息:在线版本包含补充资料,下载地址:10.1007/s43657-021-00024-z。
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