Knocking Down CDKN2A in 3D hiPSC-Derived ...
Document type :
Article dans une revue scientifique: Article original
DOI :
Title :
Knocking Down CDKN2A in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process
Author(s) :
Kahoul, Yasmina [Auteur]
Yao, Xi [Auteur]
Oger, Frédérik [Auteur]
Moreno, Maeva [Auteur]
Amanzougarene, Souhila [Auteur]
Derhourhi, Mehdi [Auteur]
Durand, Emmanuelle [Auteur]
Boutry, Raphael [Auteur]
Bonnefond, Amelie [Auteur]
Froguel, Philippe [Auteur]
Dani, Christian [Auteur]
Institut de Biologie Valrose [IBV]
Annicotte, Jean-Sébastien [Auteur correspondant]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Breton, Christophe [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Yao, Xi [Auteur]
Oger, Frédérik [Auteur]
Moreno, Maeva [Auteur]
Amanzougarene, Souhila [Auteur]
Derhourhi, Mehdi [Auteur]

Durand, Emmanuelle [Auteur]
Boutry, Raphael [Auteur]
Bonnefond, Amelie [Auteur]

Froguel, Philippe [Auteur]

Dani, Christian [Auteur]
Institut de Biologie Valrose [IBV]
Annicotte, Jean-Sébastien [Auteur correspondant]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Breton, Christophe [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Journal title :
Cells
Pages :
870
Publisher :
MDPI
Publication date :
2023-03
ISSN :
2073-4409
English keyword(s) :
adipocytes
brown adipose progenitor
browning
3D culture
CDKN2A
UCP1
thermogenesis
brown adipose progenitor
browning
3D culture
CDKN2A
UCP1
thermogenesis
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
ANR Project :
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