Influence of CPM-dependent sorting on the multi-omics profile of hepatocyte-like cells matured in microscale biochips
2022
Danoy, Mathieu | Poulain, Stéphane | Scheidecker, Benedikt | Jellali, Rachid | Tauran, Yannick | Leduc, Marjorie | Bruce, Johanna | Gilard, Francoise | Gakiere, Bertrand | Arakawa, Hiroshi | Kato, Yukio | Kim, Soo Hyeon | Kido, Taketomo | Miyajima, Atsushi | Sakai, Yasuyuki | Leclerc, Eric | Institute of Industrial Science [Tokyo] (IIS) ; University of Tokyo [Tokyo] = Tōkyō teikoku daigaku (UTokyo) | Graduate School of Engineering [The Univ of Tokyo] (UTokyo) ; University of Tokyo [Tokyo] = Tōkyō teikoku daigaku (UTokyo) | Biomécanique et Bioingénierie (BMBI) ; Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS) | Laboratoire des Multimatériaux et Interfaces (LMI) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) | Plateforme protéomique 3P5 [Institut Cochin] (3P5) ; Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) | Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)) ; Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Kanazawa University (KU) | University of Tokyo [Tokyo] = Tōkyō teikoku daigaku (UTokyo) | Laboratory for Integrated Micro Mechatronics Systems (LIMMS) ; University of Tokyo [Tokyo] = Tōkyō teikoku daigaku (UTokyo)-Centre National de la Recherche Scientifique (CNRS) | Japan Society for the Promotion of Science (JSPS) Grant-in-aid for Scientific Research (S) 16H06328. | ANR-16-RHUS-0005,iLite,iLite(2016)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. Liver modeling in disease via advanced in vitro physiological tissues remains a challenging issue, yet crucial for the future development of relevant tools for drug screening. In that regard, advanced technics such as human induced Pluripotent Stem Cells (hiPSCs) and organ-on-chip are promising technologies for the relevant reproduction of the in vivo micro physiology in in vitro culture conditions. In the present work, the maturation of carboxypeptidase M positive (CPM+) Hepatocyte-Like-Cells (HLCs) in microfluidic culture conditions was investigated. hiPSCs were differentiated in culture dishes until sorting and further amplified until seeding in biochips. After 2 weeks of maturation in biochips, evaluation of the cell metabolism was performed, and samples were collected for characterization via RNA sequencing, proteomics and metabolomics. The omics profile of biochips loaded with CPM+ HLCs was then compared with the one of previously cultured biochips loaded with unsorted HLCs. CPM+ HLCs presented advanced liver characteristics in terms of a higher activity of important Transcriptions Factors (TFs) such as HNF1, HNF4A, and CEBP/A, of the upregulation of steroids/corticoids-related nuclear receptors (FXR, NR3C2, NR4A1 genes), of phase I, and phase II metabolism genes (CYP1A1, CYP1B1, CYP2C18, CYP27A1, several UGT, SULT and GST genes). Further differences in the cellular reorganization, in the lipids and steroids metabolisms, in the OXPHOS respiration and in the expression of TGFβ signaling were also observed. The present study introduces a novel protocol using advances hiPSCs differentiation and sorting methods as well as the organ-on-chip technology to highlight important in vitro liver regeneration and hepatic maturation processes.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique