2011-10-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657104摘要：婦女的生殖潛能與其卵巢裡的卵子數目有密切相關性。我們早已熟知許多婦女的生殖相關疾病是源於生殖細胞（也就是卵子）的質或量缺陷所致。近年來，多能性幹細胞（pluripotent stem cells）包括人類胚胎幹細胞（hES cells）與人類誘導型多能幹細胞（iPS cells）逐漸成為可用來培育具有臨床應用價值之細胞（包括生殖細胞）的重要源頭細胞；這些幹細胞產物將來也許可以用於移植治療與藥物或毒物測試平台之用。因此建立一種有效的技術來誘導多能性幹細胞發育為生殖細胞（尤其是卵子），將可以提供一個極有用的平台來探討女性生殖細胞發育的調節，以及未來的臨床應用。既然人類生殖細胞的發育是受到其壁龕（niche）環境中所產生的許多因子的調節，因此我們計畫要操縱多能性幹細胞本身，以及其壁龕環境來改善生殖細胞之發育。特別是我們也要建立卵巢早發衰竭患者之誘導型多能幹細胞，來測試這個假說，也就是使用自體多能幹細胞來建立生殖細胞的可能性。此子計畫有三個特定目標：一是建立卵巢早發衰竭患者之誘導型多能幹細胞；二是操縱壁龕環境來改善人類胚胎幹細胞與誘導型多能幹細胞發育為生殖細胞；三是轉殖多能幹細胞株來促其發育為生殖細胞。我們期待這個研究可以建立最佳的壁龕環境與理想的幹細胞株，來有效誘導生殖細胞的建立，相信此研究也可以建立數株卵巢早發衰竭患者之誘導型多能幹細胞。根據這個團隊過去大量的經驗與相關研究報告，我們可以預期此計畫之執行可以產生許多有用的科學訊息與臨床應用指標。<br> Abstract: Female reproductive potential is limited by the restricted number of eggs available in the ovaries. It has been known that a number of reproductive diseases originated from defective quality or quantity of germ cells. Recently pluripotent stem cells, including human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells, are becoming potentially useful sources of stem cells for deriving clinically applicable cell lineages (including germ cells) for transplantation therapy. Therefore a robust system to induce pluripotent stem cells to germ cells (especially oocytes) will provide an effective platform to study the regulation of female germ cell formation and hopefully for future clinical application. Since the development of human germ cells are regulated by a combination of factors released from the niche environments, we plan to improve the efficiency of germ cell development, through the manipulation of pluripotent stem cells and also the niche environments. Specifically we will also derive premature ovarian failure (POF) patient-specific hiPS cells for germ cell development, hoping that the hypothetical concept of producing tailor-made female germ cells can be tested. There are three Specific Aims for this subproject, which include Aim 1, the derivation of POF patient-specific hiPS cells; Aim 2, manipulation of the niche environments to improve the differentiation of hES and hiPS cells towards germ cell lineage; Aim 3, genetic manipulation of pluripotent stem cells for germ cell development. It is anticipated that this study can establish optimal niche environments and/or optimal genetic manipulation of the pluripotent stem cells for effective induction towards germ cells with appropriate meiosis and epigenetic reprogramming. Hopefully several lines of POF patient-specific hiPS cells will also be derived and characterized for future study. According to the extensive past experience and report on this issue by this team, one can anticipate significant production of useful information through the future conduction of this subproject.人類誘導型多能幹細胞生殖細胞human induced pluripotent stem (hiPS) cellsgerm cells