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

Abstract 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 li...

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Autores principales:	Kyle M. Schachtschneider, Yingkai Liu, Suvi Mäkeläinen, Ole Madsen, Laurie A. Rund, Martien A. M. Groenen, Lawrence B. Schook
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7314ba9aa5ac4be891d578f92f1235cc
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spelling	oai:doaj.org-article:7314ba9aa5ac4be891d578f92f1235cc2021-12-02T15:06:16ZOncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas10.1038/s41598-017-02912-92045-2322https://doaj.org/article/7314ba9aa5ac4be891d578f92f1235cc2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02912-9https://doaj.org/toc/2045-2322Abstract 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.Kyle M. SchachtschneiderYingkai LiuSuvi MäkeläinenOle MadsenLaurie A. RundMartien A. M. GroenenLawrence B. SchookNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyle M. Schachtschneider Yingkai Liu Suvi Mäkeläinen Ole Madsen Laurie A. Rund Martien A. M. Groenen Lawrence B. Schook Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
description	Abstract 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.
format	article
author	Kyle M. Schachtschneider Yingkai Liu Suvi Mäkeläinen Ole Madsen Laurie A. Rund Martien A. M. Groenen Lawrence B. Schook
author_facet	Kyle M. Schachtschneider Yingkai Liu Suvi Mäkeläinen Ole Madsen Laurie A. Rund Martien A. M. Groenen Lawrence B. Schook
author_sort	Kyle M. Schachtschneider
title	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_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_sort	oncopig soft-tissue sarcomas recapitulate key transcriptional features of human sarcomas
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7314ba9aa5ac4be891d578f92f1235cc
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Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas

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