Identification of the cell-of-origin of clear cell sarcoma utilizing iPS cell technology and development of novel molecular therapy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10437
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Gifu University
• Principal Investigator: Ohno Takatoshi 岐阜大学, 大学院医学系研究科, 非常勤講師 (60281052)
• Co-Investigator(Kenkyū-buntansha): 秋山 治彦 岐阜大学, 大学院医学系研究科, 教授 (60402830) ; 永野 昭仁 岐阜大学, 医学部附属病院, 講師 (60422721)
• Research Collaborator: Yamada Yasuhiro 京都大学, iPS細胞研究所, 教授 ; Komura Shingo 岐阜大学, 医学部附属病院, 助教
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 明細胞肉腫 / EWS/ATF1 / iPS細胞 / 起源細胞

Outline of Final Research Achievements

We established sarcoma-derived induced pluripotent stem cells (iPSCs) from EWS/ATF1-induced sarcoma cell line. We re-differentiated iPSCs into all kinds of somatic cells by generating sarcoma iPSCs-derived chimeric mice. Upon reinduction of EWS/ATF1 in somatic cells, sarcomas specifically developed around subcutaneous tissue and fascia. As a result of histological analysis and lineage tracing experiment, we revealed that Mpz and Tppp3 lineages were origin of EWS/ATF1-induced sarcomas. Moreover, microarray and ChIP-sequencing experiment revealed that transcriptional response against EWS/ATF1 expression was different from each cell type, and it depended on cell-type specific EWS/ATF1 binding to the genome.

Free Research Field

整形外科学