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与多能干细胞来源的心肌细胞相比的人类胎儿心脏转录组。

Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells.

作者信息

van den Berg Cathelijne W, Okawa Satoshi, Chuva de Sousa Lopes Susana M, van Iperen Liesbeth, Passier Robert, Braam Stefan R, Tertoolen Leon G, del Sol Antonio, Davis Richard P, Mummery Christine L

机构信息

Dept. of Anatomy & Embryology, Leiden University Medical Center, Einthovenweg 20, Leiden 2333 ZC, The Netherlands.

Computational Biology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6, Avenue du Swing, Belvaux L-4367, Luxembourg.

出版信息

Development. 2015 Sep 15;142(18):3231-8. doi: 10.1242/dev.123810. Epub 2015 Jul 24.

Abstract

Differentiated derivatives of human pluripotent stem cells (hPSCs) are often considered immature because they resemble foetal cells more than adult, with hPSC-derived cardiomyocytes (hPSC-CMs) being no exception. Many functional features of these cardiomyocytes, such as their cell morphology, electrophysiological characteristics, sarcomere organization and contraction force, are underdeveloped compared with adult cardiomyocytes. However, relatively little is known about how their gene expression profiles compare with the human foetal heart, in part because of the paucity of data on the human foetal heart at different stages of development. Here, we collected samples of matched ventricles and atria from human foetuses during the first and second trimester of development. This presented a rare opportunity to perform gene expression analysis on the individual chambers of the heart at various stages of development, allowing us to identify not only genes involved in the formation of the heart, but also specific genes upregulated in each of the four chambers and at different stages of development. The data showed that hPSC-CMs had a gene expression profile similar to first trimester foetal heart, but after culture in conditions shown previously to induce maturation, they cluster closer to the second trimester foetal heart samples. In summary, we demonstrate how the gene expression profiles of human foetal heart samples can be used for benchmarking hPSC-CMs and also contribute to determining their equivalent stage of development.

摘要

人类多能干细胞(hPSC)分化而来的衍生物通常被认为是不成熟的,因为它们更类似于胎儿细胞而非成体细胞,源自hPSC的心肌细胞(hPSC-CM)也不例外。与成年心肌细胞相比,这些心肌细胞的许多功能特征,如细胞形态、电生理特性、肌节组织和收缩力等,都发育不全。然而,对于它们的基因表达谱与人类胎儿心脏的比较情况,我们了解得相对较少,部分原因是关于人类胎儿心脏在不同发育阶段的数据匮乏。在此,我们收集了发育第一和第二孕期人类胎儿匹配的心室和心房样本。这提供了一个难得的机会,可对心脏各个发育阶段的单个腔室进行基因表达分析,使我们不仅能够识别参与心脏形成的基因,还能确定在四个腔室以及不同发育阶段各自上调的特定基因。数据显示,hPSC-CM的基因表达谱与孕早期胎儿心脏相似,但在先前已证明可诱导成熟的条件下培养后,它们更接近于孕中期胎儿心脏样本。总之,我们展示了人类胎儿心脏样本的基因表达谱如何可用于对hPSC-CM进行基准测试,也有助于确定它们相当的发育阶段。

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