@article{b9320483a7aa4acab6e7c206034dbc40,
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.",
author = "Metta D{\"u}lk and Gy{\"o}ngyi Kudlik and Anna Fekete and D{\'a}vid Ernszt and Kriszti{\'a}n Kvell and Pongr{\'a}cz, {Judit E.} and Mero, {Bal{\'a}zs L.} and B{\'a}lint Szeder and L{\'a}szl{\'o} Radnai and Mikl{\'o}s Geiszt and Cs{\'e}csy, {Dalma E.} and Tam{\'a}s Kov{\'a}cs and Ferenc Uher and {\'A}rp{\'a}d L{\'a}nyi and Virag Vas and L{\'a}szl{\'o} Buday",
note = "Funding Information: We are grateful to Ferenc Erd?lyi and Zsuzsanna Erd?lyi (Animal House, Institute of Experimental Medicine, Hungarian Academy of Sciences) for the excellent animal house service. We thank Adrienn Gy?ngy?si ?s Eszter Boldizs?r for their kind help by the adiposity examination of the mice. We thank Zita Haidar for the daily support of the laboratory work. We thank for David Sz?ts for carefully reading the manuscript. The work was supported by a grant from the Hungarian Research Fund OTKA (K83867), the MedinProt Program of the Hungarian Academy of Sciences (L.B.), and the {"}Lend?let{"} Grant from the Hungarian Academy of Sciences (L.B. and M.G.). L.R. and V.V. were supported by a post-doctoral fellowship program by the Hungarian Academy of Sciences. This work of V.V. was supported by J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences. Publisher Copyright: {\textcopyright} 2016 The Author(s). Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",
year = "2016",
month = oct,
day = "6",
doi = "10.1038/srep34280",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}