Elucidating X chromosome regulation in human cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Genome biology
• Research Institution: Osaka Medical College
• Principal Investigator: Tomoda Kiichiro 大阪医科大学, 医学部, 非常勤講師 (50362843)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: X染色体不活性化 / X染色体再活性化 / ヒトiPS細胞 / マウス多能性幹細胞 / 着床 / 胚盤胞 / 初期発生 / 胚性ゲノム活性化

Outline of Final Research Achievements

In this study, we tried to establish female human induced pluripotent stem (iPS) cell lines with two X chromosomes active (XaXa) to elucidate X chromosome regulation in humans cells. To generate XaXa hiPS lines reproducibly, we optimized a culture condition using mouse pluripotent stem cells. We found that self-organizing 3D floating cysts emerged under one condition tested. The cysts exhibited a blastocoel-like cavity. Their outer cells expressed trophectoderm (TE) lineage markers, and inner cells expressed pluripotency markers. Thus, they resemble natural blastocysts. We named the cysts induced blastocyst-like cysts (iBLCs). When transplanted to pseudopregnant mouse uteruses, they implanted in the uteruses. Then, they induced decidualization and exhibited growth and development before resorption. These results demonstrate that they are implantation-competent. iBLCs may contribute to the understanding of molecular mechanisms that underpin totipotency, embryogenesis, and implantation.

Free Research Field

多能性幹細胞

Academic Significance and Societal Importance of the Research Achievements

マウス多能性幹細胞を用いてヒト人工多能性幹細胞（iPS 細胞）の培養条件最適化を行った。我々の開発した培養条件下で、受精後に見られる遺伝子発現変化を伴い、着床する能力を持つ胚盤胞に類似した構造（誘導性胚盤胞様嚢胞、iBLC）が形成された。この実験系は、ヒトiPS細胞培養条件の改良のみならず、受精後の初期発生の解明のための有用なモデルになると考えられる 。