title: A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells.
abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders.
authors.affiliation: CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lo Cicero
authors.affiliation: CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Jaskowiak
authors.affiliation: CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Egesipe
authors.affiliation: CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
authors.forename: Johana
authors.initials: J
authors.lastname: Tournois
authors.affiliation: CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brinon
authors.affiliation: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Largo Marques de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Pitrez
authors.affiliation: CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Largo Marques de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
authors.affiliation: Aix Marseille Université, UMR S 910: Génétique médicale et génomique fonctionnelle, Faculté de médecine Timone, Marseille, France.|INSERM, UMR S 910: Génétique médicale et génomique fonctionnelle, Faculté de médecine, Marseille, France.
authors.forename: Annachiara
authors.initials: A
authors.lastname: de Sandre-Giovannoli
authors.affiliation: Aix Marseille Université, UMR S 910: Génétique médicale et génomique fonctionnelle, Faculté de médecine Timone, Marseille, France.|INSERM, UMR S 910: Génétique médicale et génomique fonctionnelle, Faculté de médecine, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levy
authors.affiliation: CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.|UEVE, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Nissan
mesh_terms: D019588:Aging, Premature / Q000628:therapy*; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D005786:Gene Expression Regulation; D048091:Guided Tissue Regeneration; D057166:High-Throughput Screening Assays; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D015474:Isotretinoin / Q000494:pharmacology / Q000627:therapeutic use*; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010012:Osteogenesis; D011371:Progeria / Q000628:therapy*; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D034904:Lamin Type A; C090764:prelamin A; D014212:Tretinoin; D000469:Alkaline Phosphatase; D015474:Isotretinoin