A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use

被引:15
作者
Ardisasmita, Arif Ibrahim [1 ,2 ,3 ]
Schene, Imre F. [1 ,2 ,3 ]
Joore, Indi P. [1 ,2 ,3 ]
Kok, Gautam [1 ,2 ,3 ]
Hendriks, Delilah [4 ]
Artegiani, Benedetta [5 ]
Mokry, Michal [1 ,6 ,7 ]
Nieuwenhuis, Edward E. S. [1 ,8 ]
Fuchs, Sabine A. [2 ,3 ]
机构
[1] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Div Pediat Gastroenterol, NL-3584 EA Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Metab Dis, NL-3584 EA Utrecht, Netherlands
[3] Regenerat Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands
[4] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands
[5] Princess Maxima Ctr, NL-3584 CS Utrecht, Netherlands
[6] Univ Med Ctr, Lab Clin Chem & Haematol, Utrecht, Netherlands
[7] Univ Med Ctr, Dept Cardiol, Utrecht, Netherlands
[8] Univ Coll Roosevelt, Dept Sci, NL-4331 CB Middelburg, Netherlands
关键词
PLURIPOTENT STEM-CELLS; METABOLICALLY FUNCTIONING HEPATOCYTES; LIVER REPOPULATION; GENE-EXPRESSION; DIFFERENTIATION; GENERATION; EXPANSION; CULTURE; SPECIFICATION; FIBROBLASTS;
D O I
10.1038/s42003-022-04046-9
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
A systematic comparison of transcriptomes across different hepatocyte models provides a valuable resource to determine the most suitable model for a particular application or research question. The myriad of available hepatocyte in vitro models provides researchers the possibility to select hepatocyte-like cells (HLCs) for specific research goals. However, direct comparison of hepatocyte models is currently challenging. We systematically searched the literature and compared different HLCs, but reported functions were limited to a small subset of hepatic functions. To enable a more comprehensive comparison, we developed an algorithm to compare transcriptomic data across studies that tested HLCs derived from hepatocytes, biliary cells, fibroblasts, and pluripotent stem cells, alongside primary human hepatocytes (PHHs). This revealed that no HLC covered the complete hepatic transcriptome, highlighting the importance of HLC selection. HLCs derived from hepatocytes had the highest transcriptional resemblance to PHHs regardless of the protocol, whereas the quality of fibroblasts and PSC derived HLCs varied depending on the protocol used. Finally, we developed and validated a web application (HLCompR) enabling comparison for specific pathways and addition of new HLCs. In conclusion, our comprehensive transcriptomic comparison of HLCs allows selection of HLCs for specific research questions and can guide improvements in culturing conditions.
引用
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页数:15
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