Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process
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/bei...
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/6/870 |
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| author | Yasmina Kahoul Xi Yao Frédérik Oger Maeva Moreno Souhila Amanzougarene Mehdi Derhourhi Emmanuelle Durand Raphael Boutry Amélie Bonnefond Philippe Froguel Christian Dani Jean-Sébastien Annicotte Christophe Breton |
| author_facet | Yasmina Kahoul Xi Yao Frédérik Oger Maeva Moreno Souhila Amanzougarene Mehdi Derhourhi Emmanuelle Durand Raphael Boutry Amélie Bonnefond Philippe Froguel Christian Dani Jean-Sébastien Annicotte Christophe Breton |
| author_sort | Yasmina Kahoul |
| collection | DOAJ |
| description | 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 (<i>CDKN2A</i>) 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 <i>CDKN2A</i> expression during hiPSC-BAP adipogenic differentiation and observed that knocking down <i>CDKN2A</i> 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 <i>CDKN2A</i> levels could be relevant for hiPSC-BAPs cell-based therapies. |
| first_indexed | 2024-03-11T06:47:50Z |
| format | Article |
| id | doaj.art-9ca4d84617004903a15fd6dc72ce9d4b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:47:50Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-9ca4d84617004903a15fd6dc72ce9d4b2023-11-17T10:13:02ZengMDPI AGCells2073-44092023-03-0112687010.3390/cells12060870Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning ProcessYasmina Kahoul0Xi Yao1Frédérik Oger2Maeva Moreno3Souhila Amanzougarene4Mehdi Derhourhi5Emmanuelle Durand6Raphael Boutry7Amélie Bonnefond8Philippe Froguel9Christian Dani10Jean-Sébastien Annicotte11Christophe Breton12Univ. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceFaculté de Médecine, CNRS, INSERM, iBV, Université Côte d’Azur, CEDEX 2, F-06107 Nice, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceFaculté de Médecine, CNRS, INSERM, iBV, Université Côte d’Azur, CEDEX 2, F-06107 Nice, FranceUniv. Lille, Inserm, CHU Lille, Institut Pasteur Lille, U1167 - RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement, F-59000 Lille, FranceUniv. Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1283-UMR8199-EGID, F-59000 Lille, FranceHuman 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 (<i>CDKN2A</i>) 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 <i>CDKN2A</i> expression during hiPSC-BAP adipogenic differentiation and observed that knocking down <i>CDKN2A</i> 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 <i>CDKN2A</i> levels could be relevant for hiPSC-BAPs cell-based therapies.https://www.mdpi.com/2073-4409/12/6/870human induced pluripotent stem cellsadipocytesbrown adipose progenitorbrowning3D culture<i>CDKN2A</i> |
| spellingShingle | Yasmina Kahoul Xi Yao Frédérik Oger Maeva Moreno Souhila Amanzougarene Mehdi Derhourhi Emmanuelle Durand Raphael Boutry Amélie Bonnefond Philippe Froguel Christian Dani Jean-Sébastien Annicotte Christophe Breton Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process Cells human induced pluripotent stem cells adipocytes brown adipose progenitor browning 3D culture <i>CDKN2A</i> |
| title | Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process |
| title_full | Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process |
| title_fullStr | Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process |
| title_full_unstemmed | Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process |
| title_short | Knocking Down <i>CDKN2A</i> in 3D hiPSC-Derived Brown Adipose Progenitors Potentiates Differentiation, Oxidative Metabolism and Browning Process |
| title_sort | knocking down i cdkn2a i in 3d hipsc derived brown adipose progenitors potentiates differentiation oxidative metabolism and browning process |
| topic | human induced pluripotent stem cells adipocytes brown adipose progenitor browning 3D culture <i>CDKN2A</i> |
| url | https://www.mdpi.com/2073-4409/12/6/870 |
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