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

被引：4

作者：

Danoy, Mathieu ^{[1
,2
]}

Poulain, Stephane ^{[3
]}

Jellali, Rachid ^{[4
]}

Scheidecker, Benedikt ^{[1
,2
]}

Tauran, Yannick ^{[5
]}

Leduc, Marjorie ^{[6
]}

Bruce, Johanna ^{[6
]}

Kim, Soo Hyeon ^{[3
]}

Kido, Taketomo ^{[7
]}

Miyajima, Atsushi ^{[7
]}

Sakai, Yasuyuki ^{[2
]}

Leclerc, Eric ^{[1
,4
,8
]}

机构：

[1] Univ Tokyo, Inst Ind Sci, Lab Integrated Micro Mechatron Syst, CNRS IRL 2820, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Engn, Dept Chem Syst Engn, Tokyo, Japan

[3] Univ Tokyo, Inst Ind Sci, Tokyo, Japan

[4] Sorbonne Univ, Univ Technol Compiegne, CNRS UMR 7338, Lab Biomecan & Bioingenierie, Compiegne, France

[5] Univ Lyon 1, LMI CNRS UMR5615, Villeurbanne, France

[6] Univ Paris, Inst Cochin, INSERM, CNRS,Plateforme Prote 3P5, Paris, France

[7] Univ Tokyo, Inst Quantitat Biosci, Lab Cell Growth & Differentiat, Tokyo, Japan

[8] Univ Tokyo, Inst Ind Sci, IRL 2820 LIMMS CNRSIIS, 4-6-1 Komaba, Meguro ku, Tokyo 1538505, Japan

来源：

HEPATOLOGY RESEARCH | 2023年 / 53卷 / 07期

基金：

日本学术振兴会;

关键词：

CPM plus; hepatocyte like cells; hiPSCs; liver progenitor cell; LSECs; organ on chip; proteomics; transcriptomics; zonation; GROWTH; PATHWAY; EXTRACTION; NANOCAGE;

D O I：

10.1111/hepr.13893

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

AimHepatic 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. MethodsAn 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. ResultsHepatic 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/beta-catenin, transforming growth factor-beta, mammalian target of rapamycin, hypoxia-inducible factor-1, and AMP-activated protein kinase signaling, to the metabolism of lipids, and cellular remolding were observed. ConclusionsThe 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.

引用

页码：661 / 674

页数：14

共 69 条

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