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高通量转录组谱分析揭示了人类间充质干细胞在软骨生成过程中的时间基因特征。

High-depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis.

机构信息

Department of Orthopedic Surgery, Washington University in St. Louis, St. Louis, Missouri, USA.

Shriners Hospitals for Children-St. Louis, St. Louis, Missouri, USA.

出版信息

FASEB J. 2019 Jan;33(1):358-372. doi: 10.1096/fj.201800534R. Epub 2018 Jul 9.

Abstract

Mesenchymal stem/stromal cells (MSCs) provide an attractive cell source for cartilage repair and cell therapy; however, the underlying molecular pathways that drive chondrogenesis of these populations of adult stem cells remain poorly understood. We generated a rich data set of high-throughput RNA sequencing of human MSCs throughout chondrogenesis at 6 different time points. Our data consisted of 18 libraries with 3 individual donors as biologic replicates, with each library possessing a sequencing depth of 100 million reads. Computational analyses with differential gene expression, gene ontology, and weighted gene correlation network analysis identified dynamic changes in multiple biologic pathways and, most importantly, a chondrogenic gene subset, whose functional characterization promises to further harness the potential of MSCs for cartilage tissue engineering. Furthermore, we created a graphic user interface encyclopedia built with the goal of producing an open resource of transcriptomic regulation for additional data mining and pathway analysis of the process of MSC chondrogenesis.-Huynh, N. P. T., Zhang, B., Guilak, F. High-depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis.

摘要

间充质干细胞(MSCs)为软骨修复和细胞治疗提供了有吸引力的细胞来源;然而,这些成体干细胞的软骨生成的潜在分子途径仍知之甚少。我们在 6 个不同的时间点对人类 MSCs 的整个软骨生成过程进行了高通量 RNA 测序,生成了丰富的数据集。我们的数据由 18 个文库组成,每个文库包含 3 个个体供体作为生物学重复,每个文库的测序深度为 1 亿个读数。通过差异基因表达、基因本体和加权基因相关网络分析的计算分析,确定了多个生物学途径的动态变化,最重要的是,确定了一个软骨生成基因子集,其功能特征有望进一步利用 MSCs 用于软骨组织工程。此外,我们创建了一个图形用户界面百科全书,旨在生成一个转录组调控的开放资源,用于进一步挖掘 MSC 软骨生成过程的数据挖掘和途径分析。

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