hiPSC-derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver
hiPSC-derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver
复制标题
DOI：
10.1002/jcp.27131
复制
发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Aalto-Setala, Katriina
中科院分区：
文献类型：
--
作者：
Kiamehr, Mostafa;Alexanova, Anna;Aalto-Setala, Katriina
从人诱导的多能干细胞分化而来的类肝细胞(HLCs)为研究肝脏脂代谢提供了替代原代人肝细胞(PHHs)的平台。然而，尽管HLCs具有巨大的潜力，但其脂质谱尚未被表征。在这里，我们对HLCs的脂谱和脂肪酸(FA)代谢进行了全面的研究，并与目前标准的肝细胞模型：HepG2细胞和PHHs进行了比较。我们用五种常用的方法从三个细胞系中分化出HLCs，并从基因和蛋白表达的角度对它们进行了全面的鉴定。对每种方法产生的HLC的功能性以及合成、延长和脱饱和脂肪酸的能力进行了评估。用气相色谱和质谱仪分析HLCs的脂谱和FA谱，并与PHHs和HepG2细胞的谱进行比较。HLC通过表达肝脏标志物：分泌白蛋白、脂蛋白颗粒和尿素，与PHHs相似，并在脂类和FA谱上显示出相似之处。与HepG2细胞不同，HLCs含有与PHHs含量相似的低水平溶血磷脂。此外，HLC能够有效地利用其培养液中可用的外源FA，同时将简单的脂类修饰为更复杂的脂类以满足其需求。此外，我们认为增加培养液中多不饱和脂肪酸的供应可能会对HLCs的脂谱和功能产生积极的影响。综上所述，我们的数据表明，HLCs提供了一个在分子和细胞水平上研究人类脂质稳态的功能和相关的模型。
Hepatocyte-like cells (HLCs) differentiated from human-induced pluripotent stem cells offer an alternative platform to primary human hepatocytes (PHHs) for studying the lipid metabolism of the liver. However, despite their great potential, the lipid profile of HLCs has not yet been characterized. Here, we comprehensively studied the lipid profile and fatty acid (FA) metabolism of HLCs and compared them with the current standard hepatocyte models:HepG2 cells and PHHs. We differentiated HLCs by five commonly used methods from three cell lines and thoroughly characterized them by gene and protein expression. HLCs generated by each method were assessed for their functionality and the ability to synthesize, elongate, and desaturate FAs. In addition, lipid and FA profiles of HLCs were investigated by both mass spectrometry and gas chromatography and then compared with the profiles of PHHs and HepG2 cells. HLCs resembled PHHs by expressing hepatic markers: secreting albumin, lipoprotein particles, and urea, and demonstrating similarities in their lipid and FA profile. Unlike HepG2 cells, HLCs contained low levels of lysophospholipids similar to the content of PHHs. Furthermore, HLCs were able to efficiently use the exogenous FAs available in their medium and simultaneously modify simple lipids into more complex ones to fulfill their needs. In addition, we propose that increasing the polyunsaturated FA supply of the culture medium may positively affect the lipid profile and functionality of HLCs. In conclusion, our data showed that HLCs provide a functional and relevant model to investigate human lipid homeostasis at both molecular and cellular levels.