Knocking Down CDKN2A in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process.

Autor: Kahoul Y; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Yao X; Faculté de Médecine, CNRS, INSERM, iBV, Université Côte d'Azur, CEDEX 2, F-06107 Nice, France., Oger F; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Moreno M; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Amanzougarene S; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Derhourhi M; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Durand E; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Boutry R; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France., Bonnefond A; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France.; Department of Metabolism, Imperial College London, London SW7 2BX, UK., Froguel P; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France.; Department of Metabolism, Imperial College London, London SW7 2BX, UK., Dani C; Faculté de Médecine, CNRS, INSERM, iBV, Université Côte d'Azur, CEDEX 2, F-06107 Nice, France., Annicotte JS; Univ. Lille, Inserm, CHU Lille, Institut Pasteur Lille, U1167 - RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement, F-59000 Lille, France., Breton C; Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, France.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Mar 10; Vol. 12 (6). Date of Electronic Publication: 2023 Mar 10.
DOI: 10.3390/cells12060870
Abstrakt: Human induced pluripotent stem cells (hiPSCs) have the potential to be differentiated into any cell type, making them a relevant tool for therapeutic purposes such as cell-based therapies. In particular, they show great promise for obesity treatment as they represent an unlimited source of brown/beige adipose progenitors (hiPSC-BAPs). However, the low brown/beige adipocyte differentiation potential in 2D cultures represents a strong limitation for clinical use. In adipose tissue, besides its cell cycle regulator functions, the cyclin-dependent kinase inhibitor 2A ( CDKN2A ) locus modulates the commitment of stem cells to the brown-like type fate, mature adipocyte energy metabolism and the browning of adipose tissue. Here, using a new method of hiPSC-BAPs 3D culture, via the formation of an organoid-like structure, we silenced CDKN2A expression during hiPSC-BAP adipogenic differentiation and observed that knocking down CDKN2A potentiates adipogenesis, oxidative metabolism and the browning process, resulting in brown-like adipocytes by promoting UCP1 expression and beiging markers. Our results suggest that modulating CDKN2A levels could be relevant for hiPSC-BAPs cell-based therapies.
Databáze: MEDLINE
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