TY - JOUR
T1 - A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use
AU - Ardisasmita, Arif Ibrahim
AU - Schene, Imre F
AU - Joore, Indi P
AU - Kok, Gautam
AU - Hendriks, Delilah
AU - Artegiani, Benedetta
AU - Mokry, Michal
AU - Nieuwenhuis, Edward E S
AU - Fuchs, Sabine A
N1 - Funding Information:
The study was supported by ZonMW TAS (‘Regenerating Intestinal Tissue with Stem cells’ project) and Metakids (‘Minilevertjes’ project). The study was stimulated by the national multidisciplinary collaboration United for Metabolic Diseases (UMD) to improve care for patients with metabolic diseases.
Funding Information:
The study was supported by ZonMW TAS (‘Regenerating Intestinal Tissue with Stem cells’ project) and Metakids (‘Minilevertjes’ project). The study was stimulated by the national multidisciplinary collaboration United for Metabolic Diseases (UMD) to improve care for patients with metabolic diseases.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/10/14
Y1 - 2022/10/14
N2 - 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.
AB - 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.
KW - Cell Differentiation/genetics
KW - Hepatocytes/metabolism
KW - Humans
KW - Induced Pluripotent Stem Cells/metabolism
KW - Pluripotent Stem Cells
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85140140834&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-04046-9
DO - 10.1038/s42003-022-04046-9
M3 - Article
C2 - 36241695
SN - 2399-3642
VL - 5
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 1094
ER -