2022 Fiscal Year Final Research Report

Molecular mechanisms of cell differentiation and diversity by TGF-beta family members

Planned Research

PDF

Project Area	Integrated analysis and regulation of cellular diversity
Project/Area Number	17H06326
Research Category	Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Allocation Type	Single-year Grants
Review Section	Complex systems
Research Institution	The University of Tokyo
Principal Investigator	Miyazono Kohei 東京大学, 大学院医学系研究科(医学部), 卓越教授 (90209908)
Co-Investigator(Kenkyū-buntansha)	鯉沼代造東京大学, 大学院医学系研究科(医学部), 准教授 (80375071) 森川真大帝京大学, 先端総合研究機構, 准教授 (80775833) 江幡正悟和歌山県立医科大学, 医学部, 教授 (90506726)
Project Period (FY)	2017-06-30 – 2022-03-31
Keywords	発生・分化 / シグナル伝達 / 癌
Outline of Final Research Achievements	We studied the molecular mechanisms through which highly diverse populations of cells are generated from single cells, mainly focusing on cancer cells. We identified the transcription factor PRRX1 and a TNF receptor superfamily protein as molecules involved in differentiation of glioblastoma initiating cells and studied their functions. We also investigated the mechanisms involved in malignant transformation of pancreatic and renal cancers by serial orthotopic transplantation of cancer cells into mice. In renal cell carcinoma, we found that lung metastasis is accelerated by the neutrophil-mediated aggravation of inflammation in tumor tissues. We further studied the mechanism of differentiation of non-cancer cells, such as mouse ES cells. In addition, we established a method for three-dimensional visualization of blood and lymphatic vessels and cancer cells by using tissue clearing technology, studied interactions of these cells, and introduced mathematical analysis in the system.
Free Research Field	腫瘍生物学
Academic Significance and Societal Importance of the Research Achievements	生体を構成する細胞は多様性と可塑性に富んでおり、その分化機構を明らかにすることは、初期胚の分化、種々の組織の形態形成、がんなどの疾患の病態解明に重要な役割を果たすと期待される。本研究の成果は、がんをはじめとした様々な疾患の新たな治療法の開発に寄与すると考える。