SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism

Abstract Due to redundancy with other tyrosine phosphatases, the ubiquitously expressed tyrosine phosphatase SHP-2 (encoded by Ptpn11) is not required for T cell development. However, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in the wrist. Using a fate mapping syst...

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Autores principales:	Jeffrey T. McNamara, Kelsey E. Huntington, Samantha Borys, Chathuraka T. Jayasuriya, Laurent Brossay
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a751a04443e4a1ea1e610f1904326ef
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spelling	oai:doaj.org-article:9a751a04443e4a1ea1e610f1904326ef2021-12-02T18:37:08ZSHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism10.1038/s41598-021-99339-02045-2322https://doaj.org/article/9a751a04443e4a1ea1e610f1904326ef2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99339-0https://doaj.org/toc/2045-2322Abstract Due to redundancy with other tyrosine phosphatases, the ubiquitously expressed tyrosine phosphatase SHP-2 (encoded by Ptpn11) is not required for T cell development. However, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in the wrist. Using a fate mapping system, we demonstrate that wrist tumor development correlates with increased frequency and numbers of non-hematopoietic lineage negative CD45 negative cells with a bone chondrocyte stromal cell precursor cell (BCSP) phenotype. Importantly, the BCSP subset has a history of CD4 expression and a marked wrist location tropism, explaining why the wrist is the main site of tumor development. Mechanistically, we found that in SHP-2 absence, SOX-9 is no longer regulated, leading to an uncontrolled proliferation of the BCSP subset. Altogether, these results identify a unique subset of chondrocyte precursors tightly regulated by SHP-2. These findings underscore the need for the development of methods to therapeutically target this subset of cells, which could potentially have an impact on treatment of SHP-2 dysfunction linked debilitating diseases.Jeffrey T. McNamaraKelsey E. HuntingtonSamantha BorysChathuraka T. JayasuriyaLaurent BrossayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeffrey T. McNamara Kelsey E. Huntington Samantha Borys Chathuraka T. Jayasuriya Laurent Brossay SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
description	Abstract Due to redundancy with other tyrosine phosphatases, the ubiquitously expressed tyrosine phosphatase SHP-2 (encoded by Ptpn11) is not required for T cell development. However, Ptpn11 gene deletion driven by CD4 Cre recombinase leads to cartilage tumors in the wrist. Using a fate mapping system, we demonstrate that wrist tumor development correlates with increased frequency and numbers of non-hematopoietic lineage negative CD45 negative cells with a bone chondrocyte stromal cell precursor cell (BCSP) phenotype. Importantly, the BCSP subset has a history of CD4 expression and a marked wrist location tropism, explaining why the wrist is the main site of tumor development. Mechanistically, we found that in SHP-2 absence, SOX-9 is no longer regulated, leading to an uncontrolled proliferation of the BCSP subset. Altogether, these results identify a unique subset of chondrocyte precursors tightly regulated by SHP-2. These findings underscore the need for the development of methods to therapeutically target this subset of cells, which could potentially have an impact on treatment of SHP-2 dysfunction linked debilitating diseases.
format	article
author	Jeffrey T. McNamara Kelsey E. Huntington Samantha Borys Chathuraka T. Jayasuriya Laurent Brossay
author_facet	Jeffrey T. McNamara Kelsey E. Huntington Samantha Borys Chathuraka T. Jayasuriya Laurent Brossay
author_sort	Jeffrey T. McNamara
title	SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
title_short	SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
title_full	SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
title_fullStr	SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
title_full_unstemmed	SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism
title_sort	shp-2 deletion in cd4cre expressing chondrocyte precursors leads to tumor development with wrist tropism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9a751a04443e4a1ea1e610f1904326ef
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SHP-2 deletion in CD4Cre expressing chondrocyte precursors leads to tumor development with wrist tropism

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