Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells
Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells
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DOI：
10.1161/atvbaha.117.309199
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发表时间：
2017-01-01
影响因子：
8.7
通讯作者：
Duncan, Stephen A.
中科院分区：
文献类型：
--
作者：
Pournasr, Behshad;Duncan, Stephen A.
先天性肝脏代谢缺陷是由于基因组中遗传性突变导致的单一酶的缺陷。这些疾病个别来说是罕见的，但总体来说是常见的。全基因组关联研究和DNA测序的进展帮助研究人员确定了这些疾病的潜在遗传基础。不幸的是，细胞和动物模型，准确地概括了这些先天性缺陷的肝脏代谢在实验室中一直缺乏。最近，研究人员利用分子技术从患者的体细胞中产生诱导多能干细胞。诱导多能干细胞可以分化成多种细胞类型，包括肝细胞，从而提供了一种创新的方法来解开先天性肝脏代谢缺陷的机制。此外，这种细胞模型可能为发现治疗方法提供平台。在这篇小型综述中，我们简要概述了使用多能干细胞进行此类研究的最新技术。
Inborn errors of hepatic metabolism are because of deficiencies commonly within a single enzyme as a consequence of heritable mutations in the genome. Individually such diseases are rare, but collectively they are common. Advances in genome-wide association studies and DNA sequencing have helped researchers identify the underlying genetic basis of such diseases. Unfortunately, cellular and animal models that accurately recapitulate these inborn errors of hepatic metabolism in the laboratory have been lacking. Recently, investigators have exploited molecular techniques to generate induced pluripotent stem cells from patients' somatic cells. Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. In this mini-review, we present a brief overview of the state-of-the-art in using pluripotent stem cells for such studies.