Titre :

Transcriptomic profiling analysis of the effect of palmitic acid on 3D spheroids of β-like cells derived from induced pluripotent stem cells

Auteur(s) :

Morisseau, Lisa [Auteur]
Biomécanique et Bioingénierie [BMBI]
Tokito, Fumiya [Auteur]
Graduate School of Engineering [The Univ of Tokyo] [UTokyo]
Lucas, Mathilde [Auteur]
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN]
Poulain, Stéphane [Auteur]
Institute of Industrial Science [Tokyo] [IIS]
Kim, Soo Hyeon [Auteur]
Institute of Industrial Science [Tokyo] [IIS]
Plaisance, Valérie [Auteur]
NANomatériaux pour la Santé, l’Energie et l’Environnement [NANSEE - IEMN]
Pawlowski, Valérie [Auteur]
NANomatériaux pour la Santé, l’Energie et l’Environnement [NANSEE - IEMN]
Legallais, C. [Auteur]
Biomécanique et Bioingénierie [BMBI]
Jellali, Rachid [Auteur]
Biomécanique et Bioingénierie [BMBI]
Sakai, Yasuyuki [Auteur]
Laboratory for Integrated Micro Mechatronics Systems [LIMMS]
Abderrahmani, Amar [Auteur]
NANomatériaux pour la Santé, l’Energie et l’Environnement [NANSEE - IEMN]
Leclerc, Eric [Auteur correspondant]
Laboratory for Integrated Micro Mechatronics Systems [LIMMS]

Titre de la revue :

Gene

Pagination :

148441

Éditeur :

Elsevier

Date de publication :

2024

ISSN :

0378-1119

Mot(s)-clé(s) en anglais :

β-like cells
3D spheroids
Human induced pluripotent stem cells
Palmitic acids
Transcriptomics

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Endocrinologie et métabolisme

Résumé en anglais : [en]

Type 2 diabetes (T2D) is posing a serious public health concern with a considerable impact on human life and health expenditures worldwide. The disease develops when insulin plasma level is insufficient for coping insulin ...
Lire la suite >Type 2 diabetes (T2D) is posing a serious public health concern with a considerable impact on human life and health expenditures worldwide. The disease develops when insulin plasma level is insufficient for coping insulin resistance, caused by the decline of pancreatic β-cell function and mass. In β-cells, the lipotoxicity exerted by saturated free fatty acids in particular palmitate (PA), which is chronically elevated in T2D, plays a major role in β-cell dysfunction and mass. However, there is a lack of human relevant in vitro model to identify the underlying mechanism through which palmitate induces β-cell failure. In this frame, we have previously developed a cutting-edge 3D spheroid model of β-like cells derived from human induced pluripotent stem cells. In the present work, we investigated the signaling pathways modified by palmitate in β-like cells derived spheroids. When compared to the 2D monolayer cultures, the transcriptome analysis (FDR set at 0.1) revealed that the 3D spheroids upregulated the pancreatic markers (such as GCG, IAPP genes), lipids metabolism and transporters (CD36, HMGSC2 genes), glucose transporter (SLC2A6). Then, the 3D spheroids are exposed to PA 0.5 mM for 72 h. The differential analysis demonstrated that 32 transcription factors and 135 target genes were mainly modulated (FDR set at 0.1) including the upregulation of lipid and carbohydrates metabolism (HMGSC2, LDHA, GLUT3), fibrin metabolism (FGG, FGB), apoptosis (CASP7). The pathway analysis using the 135 selected targets extracted the fibrin related biological process and wound healing in 3D PA treated conditions. An overall pathway gene set enrichment analysis, performed on the overall gene set (with pathway significance cutoff at 0.2), highlighted that PA perturbs the citrate cycle, FOXO signaling and Hippo signaling as observed in human islets studies. Additional RT-PCR confirmed induction of inflammatory (IGFBP1, IGFBP3) and cell growth (CCND1, Ki67) pathways by PA. All these changes were associated with unaffected glucose-stimulated insulin secretion (GSIS), suggesting that they precede the defect of insulin secretion and death induced by PA. Overall, we believe that our data demonstrate the potential of our spheroid 3D islet-like cells to investigate the pancreatic-like response to diabetogenic environment.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520

Source :

Harvested from HAL