@article{3852440d6ce74af9a6673c6fa3bc9794,
title = "Osteogenic transdifferentiation of primary human fibroblasts to osteoblast-like cells with human platelet lysate",
abstract = "Inherited bone disorders account for about 10% of documented Mendelian disorders and are associated with high financial burden. Their study requires osteoblasts which play a critical role in regulating the development and maintenance of bone tissue. However, bone tissue is not always available from patients. We developed a highly efficient platelet lysate-based approach to directly transdifferentiate skin-derived human fibroblasts to osteoblast-like cells. We extensively characterized our in vitro model by examining the expression of osteoblast-specific markers during the transdifferentiation process both at the mRNA and protein level. The transdifferentiated osteoblast-like cells showed significantly increased expression of a panel of osteogenic markers. Mineral deposition and ALP activity were also shown, confirming their osteogenic properties. RNA-seq analysis allowed the global study of changes in the transcriptome of the transdifferentiated cells. The transdifferentiated cells clustered separately from the primary fibroblasts with regard to the significantly upregulated genes indicating a distinct transcriptome profile; transdifferentiated osteoblasts also showed significant enrichment in gene expression related to skeletal development and bone mineralization. Our presented in vitro model may potentially contribute to the prospect of studying osteoblast-dependent disorders in patient-derived cells.",
author = "Cayami, {Ferdy K.} and Lauria Claeys and {de Ruiter}, Ruben and Smilde, {Bernard J.} and Lisanne Wisse and Natalija Bogunovic and Elise Riesebos and Lyra Eken and Irsan Kooi and Sistermans, {Erik A.} and Nathalie Bravenboer and Gerard Pals and Faradz, {Sultana M. H.} and Daoud Sie and Eekhoff, {E. Marelise W.} and Dimitra Micha",
note = "Funding Information: We gratefully acknowledge the healthy volunteers of this study for their contribution. The work of Dimitra Micha, Lauria Claeys and Gerard Pals was kindly funded by the Horstingstuit foundation. The work of Dimitra Micha was also funded by the Amsterdam Movement Sciences Innovation call grant. We would like to thank Behrouz Zandieh-Doulabi, Youssef Moutouakil, Cornelis M. Semeins for their contribution. Ferdy K Cayami is a recipient of the Directorate of Higher Education Overseas Scholarship–Dikti Scholarship, Ministry of National Education, Republic of Indonesia. The work of Ferdy K Cayami was funded by the High Reputation of International Publication Grant of Diponegoro University, Republic of Indonesia (No.329‐113/UN7.P4.3/PP/2019). Funding Information: We gratefully acknowledge the healthy volunteers of this study for their contribution. The work of Dimitra Micha, Lauria Claeys and Gerard Pals was kindly funded by the Horstingstuit foundation. The work of Dimitra Micha was also funded by the Amsterdam Movement Sciences Innovation call grant. We would like to thank Behrouz Zandieh-Doulabi, Youssef Moutouakil, Cornelis M. Semeins for their contribution. Ferdy K Cayami is a recipient of the Directorate of Higher Education Overseas Scholarship–Dikti Scholarship, Ministry of National Education, Republic of Indonesia. The work of Ferdy K Cayami was funded by the High Reputation of International Publication Grant of Diponegoro University, Republic of Indonesia (No.329‐113/UN7.P4.3/PP/2019). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "https://doi.org/10.1038/s41598-022-18512-1",
language = "English",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}