Calcitriol promotes the maturation of hepatocyte-like cells derived from human pluripotent stem cells
Calcitriol promotes the maturation of hepatocyte-like cells derived from human pluripotent stem cells
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骨化三醇促进源自人多能干细胞的肝细胞样细胞的成熟
DOI：
10.1016/j.jsbmb.2021.105881
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发表时间：
2021-03
影响因子：
4.1
通讯作者：
Li Yinxiong
中科院分区：
文献类型：
--
作者：
Yuan Fang;Wang Ning;Chen Yan;Huang Xinping;Yang Zhen;Xu Yingying;You Kai;Zhang Jiaye;Wang Guodong;Zhuang Yuanqi;Pan Tingcai;Xiong Yue;Yu Xiaorui;Yang Fan;Li Yinxiong
来源于人多能干细胞（hPSC）的人肝细胞样细胞（HLC）代表了用于肝毒性评估和药物安全性测试的有前景的细胞来源。然而，HLC的肝功能仍然显著劣于原代人肝细胞。生物活性维生素D（VD）骨化三醇促进多种类型细胞的分化，其缺乏与肝脏疾病的严重程度相关。骨化三醇是否有助于HLCs的分化需要探索。在此，我们发现补充骨化三醇改善了hPSC衍生的HLC在P450活性、尿素产生和白蛋白分泌方面的功能。此外，骨化三醇还增强了线粒体呼吸功能，增加呼吸酶复合物亚基的蛋白表达水平。进一步分析表明，骨化三醇增加了线粒体生物合成调节因子和线粒体自噬，从而改善了线粒体质量。这些功能和线粒体状况的改善依赖于维生素D受体（VDR），因为这些改善在VDR缺乏的条件下被消除。我们的发现为HLC成熟提供了一种具有成本效益的化学方法，以满足基础研究和潜在临床应用的需求。
Human hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) represent a promising cell source for the assessment of hepatotoxicity and pharmaceutical safety testing. However, the hepatic functionality of HLCs remains significantly inferior to primary human hepatocytes. The bioactive vitamin D (VD), calcitriol, promotes the differentiation of many types of cells, and its deficiency is correlated to the severity of liver diseases. Whether calcitriol contributes to the differentiation of HLCs needs to be explored. Here, we found that the supplementation of calcitriol improved the functionalities of hPSCs-derived HLCs in P450 activities, urea production, and albumin secretion. Moreover, calcitriol also enhanced mitochondrial respiratory function with increased protein expression levels of the subunit of respiratory enzyme complexes in HLCs. Further analyses showed that the mitochondrial biogenesis regulators and mitophagy were increased by calcitriol, thus improving the mitochondrial quality. These improvements in functionality and mitochondrial condition were dependent on vitamin D receptor (VDR) because the improvements were abolished under VDR-deficient conditions. Our finding provides a cost-effective chemical process for HLC maturation to meet the demand for basic research and potential clinic applications.
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影响因子：
5
作者：
Chung S;Arrell DK;Faustino RS;Terzic A;Dzeja PP
通讯作者：
Dzeja PP
DOI：
--
发表时间：
2017
期刊：
--
影响因子：
--
作者：
Anaïs Wanet;Marino Caruso;Jean-Baka Domelevo Entfellner;M. Najar;Antoine Fattaccioli;C. Demazy;Jonathan Evraerts;Hoda El-Kehdy;G. Pourcher;E. Sokal;T. Arnould;Nicki Tiffin;M. Najimi;P. Renard
通讯作者：
Anaïs Wanet;Marino Caruso;Jean-Baka Domelevo Entfellner;M. Najar;Antoine Fattaccioli;C. Demazy;Jonathan Evraerts;Hoda El-Kehdy;G. Pourcher;E. Sokal;T. Arnould;Nicki Tiffin;M. Najimi;P. Renard
影响因子：
3.7
作者：
Pereira, Sandro L.;Graos, Mario;Ramalho-Santos, Joao
通讯作者：
Ramalho-Santos, Joao
DOI：
10.1096/fasebj.22.1_supplement.1197.3
发表时间：
2008-03
期刊：
The FASEB Journal
影响因子：
--
作者：
Yau-Huei Wei;Chien‐Tsun Chen;Yu-Ru V. Shih;T. K. Kuo;O. Lee
通讯作者：
Yau-Huei Wei;Chien‐Tsun Chen;Yu-Ru V. Shih;T. K. Kuo;O. Lee
影响因子：
13.5
作者：
Petta, Salvatore;Camma, Calogero;Craxi, Antonio
通讯作者：
Craxi, Antonio