Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment
Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the imp...
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2025-01-01
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| author | Giulia Gerini Alice Traversa Fabrizio Cece Matteo Cassandri Paola Pontecorvi Simona Camero Giulia Nannini Enrico Romano Francesco Marampon Mary Anna Venneri Simona Ceccarelli Antonio Angeloni Amedeo Amedei Cinzia Marchese Francesca Megiorni |
| author_facet | Giulia Gerini Alice Traversa Fabrizio Cece Matteo Cassandri Paola Pontecorvi Simona Camero Giulia Nannini Enrico Romano Francesco Marampon Mary Anna Venneri Simona Ceccarelli Antonio Angeloni Amedeo Amedei Cinzia Marchese Francesca Megiorni |
| author_sort | Giulia Gerini |
| collection | DOAJ |
| description | Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper understanding of the molecular mechanisms underlying ASC biology is crucial to identifying key regulatory pathways that influence differentiation and enhance regenerative potential. In this study, we employed the NanoString nCounter technology, an advanced multiplexed digital counting method of RNA molecules, to comprehensively characterize differentially expressed transcripts involved in metabolic pathways at distinct time points in osteogenically differentiating ASCs treated with or without the pan-DNMT inhibitor RG108. <i>In silico</i> annotation and gene ontology analysis highlighted the activation of ethanol oxidation, ROS regulation, retinoic acid metabolism, and steroid hormone metabolism, as well as in the metabolism of lipids, amino acids, and nucleotides, and pinpointed potential new osteogenic drivers like AOX1 and ADH1A. RG108-treated cells, in addition to the upregulation of the osteogenesis-related markers RUNX2 and ALPL, showed statistically significant alterations in genes implicated in transcriptional control (MYCN, MYB, TP63, and IRF1), ethanol oxidation (ADH1C, ADH4, ADH6, and ADH7), and glucose metabolism (SLC2A3). These findings highlight the complex interplay of the metabolic, structural, and signaling pathways that orchestrate osteogenic differentiation. Furthermore, this study underscores the potential of epigenetic drugs like RG108 to enhance ASC properties, paving the way for more effective and personalized cell-based therapies for bone regeneration. |
| format | Article |
| id | doaj-art-2df3785f458c4b05b4ed7899fd57da8a |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-2df3785f458c4b05b4ed7899fd57da8a2025-01-24T13:26:49ZengMDPI AGCells2073-44092025-01-0114213510.3390/cells14020135Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug TreatmentGiulia Gerini0Alice Traversa1Fabrizio Cece2Matteo Cassandri3Paola Pontecorvi4Simona Camero5Giulia Nannini6Enrico Romano7Francesco Marampon8Mary Anna Venneri9Simona Ceccarelli10Antonio Angeloni11Amedeo Amedei12Cinzia Marchese13Francesca Megiorni14Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50121 Florence, ItalyDepartment of Sense Organs, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50121 Florence, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyAdipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper understanding of the molecular mechanisms underlying ASC biology is crucial to identifying key regulatory pathways that influence differentiation and enhance regenerative potential. In this study, we employed the NanoString nCounter technology, an advanced multiplexed digital counting method of RNA molecules, to comprehensively characterize differentially expressed transcripts involved in metabolic pathways at distinct time points in osteogenically differentiating ASCs treated with or without the pan-DNMT inhibitor RG108. <i>In silico</i> annotation and gene ontology analysis highlighted the activation of ethanol oxidation, ROS regulation, retinoic acid metabolism, and steroid hormone metabolism, as well as in the metabolism of lipids, amino acids, and nucleotides, and pinpointed potential new osteogenic drivers like AOX1 and ADH1A. RG108-treated cells, in addition to the upregulation of the osteogenesis-related markers RUNX2 and ALPL, showed statistically significant alterations in genes implicated in transcriptional control (MYCN, MYB, TP63, and IRF1), ethanol oxidation (ADH1C, ADH4, ADH6, and ADH7), and glucose metabolism (SLC2A3). These findings highlight the complex interplay of the metabolic, structural, and signaling pathways that orchestrate osteogenic differentiation. Furthermore, this study underscores the potential of epigenetic drugs like RG108 to enhance ASC properties, paving the way for more effective and personalized cell-based therapies for bone regeneration.https://www.mdpi.com/2073-4409/14/2/135adipose-derived stem cellsosteogenic differentiationDNA methyltransferase inhibitormetabolic pathways |
| spellingShingle | Giulia Gerini Alice Traversa Fabrizio Cece Matteo Cassandri Paola Pontecorvi Simona Camero Giulia Nannini Enrico Romano Francesco Marampon Mary Anna Venneri Simona Ceccarelli Antonio Angeloni Amedeo Amedei Cinzia Marchese Francesca Megiorni Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment Cells adipose-derived stem cells osteogenic differentiation DNA methyltransferase inhibitor metabolic pathways |
| title | Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment |
| title_full | Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment |
| title_fullStr | Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment |
| title_full_unstemmed | Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment |
| title_short | Deciphering the Transcriptional Metabolic Profile of Adipose-Derived Stem Cells During Osteogenic Differentiation and Epigenetic Drug Treatment |
| title_sort | deciphering the transcriptional metabolic profile of adipose derived stem cells during osteogenic differentiation and epigenetic drug treatment |
| topic | adipose-derived stem cells osteogenic differentiation DNA methyltransferase inhibitor metabolic pathways |
| url | https://www.mdpi.com/2073-4409/14/2/135 |
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