Transcriptomic and proteomic studies suggest the establishment of advanced zonation-like profiles in human-induced pluripotent stem cell-derived liver sinusoidal endothelial cells and carboxypeptidase M-positive liver progenitor cells cocultured in a fluidic microenvironment.
CPM+
LSECs
hepatocyte like cells
hiPSCs
liver progenitor cell
organ on chip
proteomics
transcriptomics
zonation
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
revised:
12
02
2023
received:
27
11
2022
accepted:
13
02
2023
medline:
4
3
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
Hepatic zonation is a physiological feature of the liver, known to be key in the regulation of the metabolism of nutrients and xenobiotics and the biotransformation of numerous substances. However, the reproduction of this phenomenon remains challenging in vitro as only part of the processes involved in the orchestration and maintenance of zonation are fully understood. The recent advances in organ-on-chip technologies, which allow for the integration of multicellular 3D tissues in a dynamic microenvironment, could offer solutions for the reproduction of zonation within a single culture vessel. An in-depth analysis of zonation-related mechanisms observed during the coculture of human-induced pluripotent stem cell (hiPSC)-derived carboxypeptidase M-positive liver progenitor cells and hiPSC-derived liver sinusoidal endothelial cells within a microfluidic biochip was carried out. Hepatic phenotypes were confirmed in terms of albumin secretion, glycogen storage, CYP450 activity, and expression of specific endothelial markers such as PECAM1, RAB5A, and CD109. Further characterization of the patterns observed in the comparison of the transcription factor motif activities, the transcriptomic signature, and the proteomic profile expressed at the inlet and the outlet of the microfluidic biochip confirmed the presence of zonation-like phenomena within the biochips. In particular, differences related to Wnt/β-catenin, transforming growth factor-β, mammalian target of rapamycin, hypoxia-inducible factor-1, and AMP-activated protein kinase signaling, to the metabolism of lipids, and cellular remolding were observed. The present study shows the interest in combining cocultures of hiPSC-derived cellular models and microfluidic technologies for reproducing in vitro complex mechanisms such as liver zonation and further incites the use of those solutions for accurate reproduction of in vivo situations.
Types de publication
Journal Article
Langues
eng
Pagination
661-674Subventions
Organisme : JSPS Grant-in-Aid for Scientific Research, B
ID : 22H03934
Organisme : JSPS Core-to-Core Program
ID : JPJSCCA20190006
Organisme : Agence Nationale de la Recherche
ID : ANR-16-RHUS-0005
Organisme : Japan Society for the Promotion of Science Grant-in-aid for Scientific Research, S
ID : 16H06328
Organisme : European Regional Development FundRenatech
Organisme : FEDER
Organisme : Operational Programme for Competitiveness Factors and Employment 2007-2013
Organisme : Canceropole Ile de France
Informations de copyright
© 2023 Japan Society of Hepatology.
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