Mechanisms of mesenchymal cell differentiation through cellular aggregate formation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Tsurumi University
• Principal Investigator: Nifuji Akira 鶴見大学, 歯学部, 教授 (00240747)
• Co-Investigator(Kenkyū-buntansha): 出野 尚 鶴見大学, 歯学部, 助教 (40435699) ; 江面 陽一 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50333456) ; 中島 和久 鶴見大学, 歯学部, 講師 (90252692)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 細胞分化 / 細胞凝集 / 転写因子

Outline of Final Research Achievements

The differentiation of hard tissue starts from condensed blastema formation. Using in vitro cellular differentiation of mesodermal cell lines (C1、F1G5, 10T1/2 cells), we observed that expression of lineage specific transcription factors was up-regulated along with increase in cell density. To investigate relationship between proliferation and differentiation, we infected a vector expressing G0 or G1 cell cycle stage specific fluorescent probe and isolated stable cell lines expressing the probe. We found that differentiation marker expressions and expression of the probe were not always merged at the early stage of differentiation. However, after induction of full differentiation in sphere formation, many cells expressed both signals. Thus it suggests that so-called cellular contact inhibition does not induce differentiated phenotype, but rather additional factors are required for full differentiation in the mesodermal cell differentiation.

Free Research Field

発生学

Academic Significance and Societal Importance of the Research Achievements

細胞凝集塊は、発生における組織形成に必須であると考えられている。また癌組織も進行とともに細胞凝集をつくることが知られている。細胞密度が増える過程での増殖から分化への過程についてはまだ不明な点が多い。本研究では、細胞周期のG0期ないしG1期早期特異的なプローブを用いて、３D凝集塊の形成（sphere）での分化形質発現を解析するユニークな解析法を確立した。増殖から分化への移行過程の結果は、凝集塊形成を介した発生分化機構研究のみならず、癌などの疾病研究にも応用出来るという点で、新たなアプローチを提供できると考えている。