Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells
Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal mode...
Gespeichert in:
| Veröffentlicht in: | Journal of Visualized Experiments 2018-06 (136) |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext bestellen |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 136 |
| container_start_page | |
| container_title | Journal of Visualized Experiments |
| container_volume | |
| creator | Zhou, Ruoji Xu, An Tu, Jian Liu, Mo Gingold, Julian A Zhao, Ruiying Lee, Dung-Fang |
| description | Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal model to study this malignancy. Taking advantage of iPSC methodologies, LFS-associated osteosarcoma can be successfully modeled by differentiating LFS patient iPSCs to mesenchymal stem cells (MSCs), and then to osteoblasts--the cells of origin for osteosarcomas. These LFS osteoblasts recapitulate oncogenic properties of osteosarcoma, providing an attractive model system for delineating the pathogenesis of osteosarcoma. This manuscript demonstrates a protocol for the generation of iPSCs from LFS patient fibroblasts, differentiation of iPSCs to MSCs, differentiation of MSCs to osteoblasts, and in vivo tumorigenesis using LFS osteoblasts. This iPSC disease model can be extended to identify potential biomarkers or therapeutic targets for LFS-associated osteosarcoma. |
| doi_str_mv | 10.3791/57664 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_223</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6101728</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2067139698</sourcerecordid><originalsourceid>FETCH-LOGICAL-c382t-b002a6a49902cf34cd867ee589a5b52975bd70d968424479c9090e21197395473</originalsourceid><addsrcrecordid>eNpVkUtLxDAQx4Movr-AB-lF8FJN0jTpXARZfMGKggreQjaZ1Sxtsybtgt_erruKnmaY-c1_XoQcMnpWKGDnpZJSbJBdBoLmtFKvm3_8HbKX0oxSyWlZbZMdDlCVhYBdou-Dw9q3b9lD6jAkE21oTPaSlqGxz6-j6Rtsffb02boYGsweTeex7XKH0S_QZXet6-1gH-s--nnohlz21GGTjbCu0wHZmpo64eHa7pOX66vn0W0-fri5G12Oc1tUvMsnlHIjjQCg3E4LYV0lFWJZgSknJQdVTpyiDmQluBAKLFCgyBkDVUApVLFPLla6837SoLPDFNHUeh59Y-KnDsbr_5nWv-u3sNCSUaZ4NQicrgVi-OgxdbrxyQ4rmBZDnzSnUrECJCzRkxVqY0gp4vS3DaN6-Qz9_YyBO_470y_1c_0BOFoBs7BAPQt9bIcbrau_AFXRjVg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2067139698</pqid></control><display><type>article</type><title>Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells</title><source>Journal of Visualized Experiments : JoVE</source><creator>Zhou, Ruoji ; Xu, An ; Tu, Jian ; Liu, Mo ; Gingold, Julian A ; Zhao, Ruiying ; Lee, Dung-Fang</creator><creatorcontrib>Zhou, Ruoji ; Xu, An ; Tu, Jian ; Liu, Mo ; Gingold, Julian A ; Zhao, Ruiying ; Lee, Dung-Fang</creatorcontrib><description>Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal model to study this malignancy. Taking advantage of iPSC methodologies, LFS-associated osteosarcoma can be successfully modeled by differentiating LFS patient iPSCs to mesenchymal stem cells (MSCs), and then to osteoblasts--the cells of origin for osteosarcomas. These LFS osteoblasts recapitulate oncogenic properties of osteosarcoma, providing an attractive model system for delineating the pathogenesis of osteosarcoma. This manuscript demonstrates a protocol for the generation of iPSCs from LFS patient fibroblasts, differentiation of iPSCs to MSCs, differentiation of MSCs to osteoblasts, and in vivo tumorigenesis using LFS osteoblasts. This iPSC disease model can be extended to identify potential biomarkers or therapeutic targets for LFS-associated osteosarcoma.</description><identifier>ISSN: 1940-087X</identifier><identifier>EISSN: 1940-087X</identifier><identifier>DOI: 10.3791/57664</identifier><identifier>PMID: 29985349</identifier><language>eng</language><publisher>United States: MyJove Corporation</publisher><subject>Adolescent ; Cancer Research ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Li-Fraumeni Syndrome - genetics ; Li-Fraumeni Syndrome - metabolism ; Male ; Mesenchymal Stem Cells - metabolism ; Osteosarcoma - diagnosis ; Osteosarcoma - pathology</subject><ispartof>Journal of Visualized Experiments, 2018-06 (136)</ispartof><rights>Copyright © 2018, Journal of Visualized Experiments</rights><rights>Copyright © 2018, Journal of Visualized Experiments 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-b002a6a49902cf34cd867ee589a5b52975bd70d968424479c9090e21197395473</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttps://www.jove.com/files/email_thumbs/57664.png</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101728/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101728/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,3829,27903,27904,53769,53771</link.rule.ids><linktorsrc>$$Uhttp://dx.doi.org/10.3791/57664$$EView_record_in_Journal_of_Visualized_Experiments$$FView_record_in_$$GJournal_of_Visualized_Experiments</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29985349$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Ruoji</creatorcontrib><creatorcontrib>Xu, An</creatorcontrib><creatorcontrib>Tu, Jian</creatorcontrib><creatorcontrib>Liu, Mo</creatorcontrib><creatorcontrib>Gingold, Julian A</creatorcontrib><creatorcontrib>Zhao, Ruiying</creatorcontrib><creatorcontrib>Lee, Dung-Fang</creatorcontrib><title>Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells</title><title>Journal of Visualized Experiments</title><addtitle>J Vis Exp</addtitle><description>Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal model to study this malignancy. Taking advantage of iPSC methodologies, LFS-associated osteosarcoma can be successfully modeled by differentiating LFS patient iPSCs to mesenchymal stem cells (MSCs), and then to osteoblasts--the cells of origin for osteosarcomas. These LFS osteoblasts recapitulate oncogenic properties of osteosarcoma, providing an attractive model system for delineating the pathogenesis of osteosarcoma. This manuscript demonstrates a protocol for the generation of iPSCs from LFS patient fibroblasts, differentiation of iPSCs to MSCs, differentiation of MSCs to osteoblasts, and in vivo tumorigenesis using LFS osteoblasts. This iPSC disease model can be extended to identify potential biomarkers or therapeutic targets for LFS-associated osteosarcoma.</description><subject>Adolescent</subject><subject>Cancer Research</subject><subject>Cell Differentiation</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Li-Fraumeni Syndrome - genetics</subject><subject>Li-Fraumeni Syndrome - metabolism</subject><subject>Male</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Osteosarcoma - diagnosis</subject><subject>Osteosarcoma - pathology</subject><issn>1940-087X</issn><issn>1940-087X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtLxDAQx4Movr-AB-lF8FJN0jTpXARZfMGKggreQjaZ1Sxtsybtgt_erruKnmaY-c1_XoQcMnpWKGDnpZJSbJBdBoLmtFKvm3_8HbKX0oxSyWlZbZMdDlCVhYBdou-Dw9q3b9lD6jAkE21oTPaSlqGxz6-j6Rtsffb02boYGsweTeex7XKH0S_QZXet6-1gH-s--nnohlz21GGTjbCu0wHZmpo64eHa7pOX66vn0W0-fri5G12Oc1tUvMsnlHIjjQCg3E4LYV0lFWJZgSknJQdVTpyiDmQluBAKLFCgyBkDVUApVLFPLla6837SoLPDFNHUeh59Y-KnDsbr_5nWv-u3sNCSUaZ4NQicrgVi-OgxdbrxyQ4rmBZDnzSnUrECJCzRkxVqY0gp4vS3DaN6-Qz9_YyBO_470y_1c_0BOFoBs7BAPQt9bIcbrau_AFXRjVg</recordid><startdate>20180613</startdate><enddate>20180613</enddate><creator>Zhou, Ruoji</creator><creator>Xu, An</creator><creator>Tu, Jian</creator><creator>Liu, Mo</creator><creator>Gingold, Julian A</creator><creator>Zhao, Ruiying</creator><creator>Lee, Dung-Fang</creator><general>MyJove Corporation</general><scope>AULCJ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180613</creationdate><title>Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells</title><author>Zhou, Ruoji ; Xu, An ; Tu, Jian ; Liu, Mo ; Gingold, Julian A ; Zhao, Ruiying ; Lee, Dung-Fang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-b002a6a49902cf34cd867ee589a5b52975bd70d968424479c9090e21197395473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Cancer Research</topic><topic>Cell Differentiation</topic><topic>Humans</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Li-Fraumeni Syndrome - genetics</topic><topic>Li-Fraumeni Syndrome - metabolism</topic><topic>Male</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Osteosarcoma - diagnosis</topic><topic>Osteosarcoma - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Ruoji</creatorcontrib><creatorcontrib>Xu, An</creatorcontrib><creatorcontrib>Tu, Jian</creatorcontrib><creatorcontrib>Liu, Mo</creatorcontrib><creatorcontrib>Gingold, Julian A</creatorcontrib><creatorcontrib>Zhao, Ruiying</creatorcontrib><creatorcontrib>Lee, Dung-Fang</creatorcontrib><collection>JoVE Journal: Cancer Research</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of Visualized Experiments</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Zhou, Ruoji</au><au>Xu, An</au><au>Tu, Jian</au><au>Liu, Mo</au><au>Gingold, Julian A</au><au>Zhao, Ruiying</au><au>Lee, Dung-Fang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells</atitle><jtitle>Journal of Visualized Experiments</jtitle><addtitle>J Vis Exp</addtitle><date>2018-06-13</date><risdate>2018</risdate><issue>136</issue><issn>1940-087X</issn><eissn>1940-087X</eissn><abstract>Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal model to study this malignancy. Taking advantage of iPSC methodologies, LFS-associated osteosarcoma can be successfully modeled by differentiating LFS patient iPSCs to mesenchymal stem cells (MSCs), and then to osteoblasts--the cells of origin for osteosarcomas. These LFS osteoblasts recapitulate oncogenic properties of osteosarcoma, providing an attractive model system for delineating the pathogenesis of osteosarcoma. This manuscript demonstrates a protocol for the generation of iPSCs from LFS patient fibroblasts, differentiation of iPSCs to MSCs, differentiation of MSCs to osteoblasts, and in vivo tumorigenesis using LFS osteoblasts. This iPSC disease model can be extended to identify potential biomarkers or therapeutic targets for LFS-associated osteosarcoma.</abstract><cop>United States</cop><pub>MyJove Corporation</pub><pmid>29985349</pmid><doi>10.3791/57664</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext_linktorsrc |
| identifier | ISSN: 1940-087X |
| ispartof | Journal of Visualized Experiments, 2018-06 (136) |
| issn | 1940-087X 1940-087X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6101728 |
| source | Journal of Visualized Experiments : JoVE |
| subjects | Adolescent Cancer Research Cell Differentiation Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Li-Fraumeni Syndrome - genetics Li-Fraumeni Syndrome - metabolism Male Mesenchymal Stem Cells - metabolism Osteosarcoma - diagnosis Osteosarcoma - pathology |
| title | Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T03%3A49%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_223&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Modeling%20Osteosarcoma%20Using%20Li-Fraumeni%20Syndrome%20Patient-derived%20Induced%20Pluripotent%20Stem%20Cells&rft.jtitle=Journal%20of%20Visualized%20Experiments&rft.au=Zhou,%20Ruoji&rft.date=2018-06-13&rft.issue=136&rft.issn=1940-087X&rft.eissn=1940-087X&rft_id=info:doi/10.3791/57664&rft_dat=%3Cproquest_223%3E2067139698%3C/proquest_223%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2067139698&rft_id=info:pmid/29985349&rfr_iscdi=true |