title: The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages.
abstract: The commitment steps of mesenchymal stromal cells (MSCs) to adipogenic and other lineages have been widely studied but not fully understood. Therefore, it is critical to understand which molecules contribute to the conversion of stem cells into differentiated cells. The scaffold protein Tks4 plays a role in podosome formation, EGFR signaling and ROS production. Dysfunction of Tks4 causes a hereditary disease called Frank-ter Haar syndrome with a variety of defects concerning certain mesenchymal tissues (bone, fat and cartilage) throughout embryogenic and postnatal development. In this study, we aimed to analyze how the mutation of Tks4 affects the differentiation potential of multipotent bone marrow MSCs (BM-MSCs). We generated a Tks4 knock-out mouse strain on C57Bl/6 background, and characterized BM-MSCs isolated from wild type and Tks4-/-mice to evaluate their differentiation. Tks4-/-BM-MSCs had reduced ability to differentiate into osteogenic and adipogenic lineages compared to wild type. Studying the expression profile of a panel of lipid-regulated genes during adipogenic induction revealed that the expression of adipogenic transcription factors, genes responsible for lipid droplet formation, sterol and fatty acid metabolism was delayed or reduced in Tks4-/-BM-MSCs. Taken together, these results establish a novel function for Tks4 in the regulation of MSC differentiation.
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Metta
authors.initials: M
authors.lastname: Dülk
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Kudlik
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Fekete
authors.affiliation: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, Hungary.|Szentagothai Research Center, University of Pecs, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Ernszt
authors.affiliation: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, Hungary.|Szentagothai Research Center, University of Pecs, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Kvell
authors.affiliation: Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, Hungary.|Szentagothai Research Center, University of Pecs, Hungary.
authors.forename: Judit E
authors.initials: JE
authors.lastname: Pongrácz
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Balázs L
authors.initials: BL
authors.lastname: Merő
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Szeder
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Radnai
authors.affiliation: Department of Physiology, Semmelweis University Medical School, Budapest, Hungary.|"Momentum" Peroxidase Enzyme Research Group of the Semmelweis University and the Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Geiszt
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Dalma E
authors.initials: DE
authors.lastname: Csécsy
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kovács
authors.affiliation: Stem Cell Biology, National Blood Service, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Uher
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Lányi
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Virag
authors.initials: V
authors.lastname: Vas
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.|Department of Medical Chemistry, Semmelweis University Medical School, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Buday
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism; D002658:Developmental Disabilities / Q000235:genetics / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010009:Osteochondrodysplasias / Q000151:congenital / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; C541985:Tks4 protein, mouse