Epigenetic modifications for reprogramming and chimeric competency of cells.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04796
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Kindai University
• Principal Investigator: Okamura Daiji 近畿大学, 農学部, 講師 (80393263)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: マウス / 始原生殖細胞 / エピジェネティック / 再プログラム化 / 多能性幹細胞 / EG細胞 / ビタミンC / メチル化

Outline of Final Research Achievements

In this study, we examined the effect of Vitamin-C on freshly isolated PGCs. Vitamin-C, also known as L-ascorbic acid, has recently gained considerable attention largely due to its role in a Tet-dependent manner. This promoted us to test Vitamin-C’s direct effect on freshly isolated in vivo PGCs. To our surprise, while there was no visible colony observed in control culture, Vitamin-C supplementation alone led to the emergence of alkaline phosphatase positive colonies and subsequently the derivation of stable cell line from freshly isolated PGCs. We designated this newly derived cell line as VcPGCs. To our surprise, these cells can be propagated indefinitely in vitro and demonstrated pluripotency using teratoma formation assay. More interestingly, the pluripotent cell lines generated with Vitamine-C share distinct features compared to conventional EGCs and thus may represent a distinct pluripotent state arising from the germline.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

「細胞の再プログラム化」に目を向けてみると、現在までのところ、iPS細胞への初期化プロセスにはエピジェネティック修飾の変化が大きな役割を担っていることが示唆されている。しかしこれまでに「エピジェネティック修飾の変化を誘発する」ことのみで細胞の初期化を実現した例は無く、今回のDNA脱メチル化に機能するビタミンCの添加のみによるマウス始原生殖細胞の再プログラム化という現象は、まだその多くが謎に包まれている「細胞の初期化プログラム」を理解する上で、非常に有用なモデルに成るものと期待される。