Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas

Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines and a...

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Autores principales: Schachtschneider, Kyle M., Liu, Yingkai, Mäkeläinen, Suvi, Madsen, Ole, Rund, Laurie A., Groenen, Martien A. M., Schook, Lawrence B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453942/
https://www.ncbi.nlm.nih.gov/pubmed/28572589
http://dx.doi.org/10.1038/s41598-017-02912-9
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author Schachtschneider, Kyle M.
Liu, Yingkai
Mäkeläinen, Suvi
Madsen, Ole
Rund, Laurie A.
Groenen, Martien A. M.
Schook, Lawrence B.
author_facet Schachtschneider, Kyle M.
Liu, Yingkai
Mäkeläinen, Suvi
Madsen, Ole
Rund, Laurie A.
Groenen, Martien A. M.
Schook, Lawrence B.
author_sort Schachtschneider, Kyle M.
collection PubMed
description Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines and animal models representative of the diverse human STS subtypes critical. Pigs represent ideal human disease models due to their similar size, anatomy, metabolism, and genetics compared to humans. The Oncopig encodes inducible KRAS (G12D) and TP53 (R167H) transgenes, allowing for STS modeling in a spatial and temporal manner. This study utilized Oncopig STS cell line (fibroblast) and tumor (leiomyosarcoma) RNA-seq data to compare Oncopig and human STS expression profiles. Altered expression of 3,360 and 7,652 genes was identified in Oncopig STS cell lines and leiomyosarcomas, respectively. Transcriptional hallmarks of human STS were observed in Oncopig STS, including altered TP53 signaling, Wnt signaling activation, and evidence of epigenetic reprogramming. Furthermore, master regulators of Oncopig STS expression were identified, including FOSL1, which was previously identified as a potential human STS therapeutic target. These results demonstrate the Oncopig STS model’s ability to mimic human STS transcriptional profiles, providing a valuable resource for sarcoma research and cell line development.
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spelling pubmed-54539422017-06-02 Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas Schachtschneider, Kyle M. Liu, Yingkai Mäkeläinen, Suvi Madsen, Ole Rund, Laurie A. Groenen, Martien A. M. Schook, Lawrence B. Sci Rep Article Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines and animal models representative of the diverse human STS subtypes critical. Pigs represent ideal human disease models due to their similar size, anatomy, metabolism, and genetics compared to humans. The Oncopig encodes inducible KRAS (G12D) and TP53 (R167H) transgenes, allowing for STS modeling in a spatial and temporal manner. This study utilized Oncopig STS cell line (fibroblast) and tumor (leiomyosarcoma) RNA-seq data to compare Oncopig and human STS expression profiles. Altered expression of 3,360 and 7,652 genes was identified in Oncopig STS cell lines and leiomyosarcomas, respectively. Transcriptional hallmarks of human STS were observed in Oncopig STS, including altered TP53 signaling, Wnt signaling activation, and evidence of epigenetic reprogramming. Furthermore, master regulators of Oncopig STS expression were identified, including FOSL1, which was previously identified as a potential human STS therapeutic target. These results demonstrate the Oncopig STS model’s ability to mimic human STS transcriptional profiles, providing a valuable resource for sarcoma research and cell line development. Nature Publishing Group UK 2017-06-01 /pmc/articles/PMC5453942/ /pubmed/28572589 http://dx.doi.org/10.1038/s41598-017-02912-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Schachtschneider, Kyle M.
Liu, Yingkai
Mäkeläinen, Suvi
Madsen, Ole
Rund, Laurie A.
Groenen, Martien A. M.
Schook, Lawrence B.
Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
title Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
title_full Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
title_fullStr Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
title_full_unstemmed Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
title_short Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
title_sort oncopig soft-tissue sarcomas recapitulate key transcriptional features of human sarcomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453942/
https://www.ncbi.nlm.nih.gov/pubmed/28572589
http://dx.doi.org/10.1038/s41598-017-02912-9
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