成果報告書詳細
管理番号20110000001424
タイトル*平成22年度中間年報 iPS細胞等幹細胞産業応用促進基盤技術開発
公開日2011/11/23
報告書年度2010 - 2010
委託先名社団法人バイオ産業情報化コンソーシアム
プロジェクト番号P08030
部署名バイオテクノロジー・医療技術部
和文要約和文要約等以下本編抜粋:1. 研究開発の内容と成果
【1】-(1) 新規多能性誘導遺伝子の探索
【1】-(1)-1. 新規iPS細胞誘導因子の探索
ヒトcDNA発現リソースから、遺伝子発現調節に関与する転写因子、シグナル伝達系遺伝子のカテゴリーに絞り、集中的にこれらの遺伝子群から新規iPS細胞誘導遺伝子の探索を行った。その際遺伝子を導入する細胞はマウス胎児線維芽細胞MEF細胞を用いている。その結果、山中因子の一つであるKlf4代替機能をもつ新規4遺伝子を発見した。この4遺伝子のうち3遺伝子G6、H8、H10はヒト線維芽細胞でもKlf4の代替機能を有しており、三胚葉分化、キメラマウス作製、ジャームライントランスミッションも確認できた。新規4遺伝子については米国仮出願を行った後、PCT出願を行った。
英文要約Title: Fundamental Research Project for Promoting Industrial Use of Stem Cells such as iPS Cells
(FY2008-FY2013)FY2010 Annual Report
This year we found several genes from the human full-length cDNA library, which are complementary to the Yamanaka factors to induce iPS cells effectively. As an alternative safe vector to the Yamanaka’s retrovirus vector system, we have developed sustainable Sendai-virus derived vector (SeVdp vector) to convey genes into somatic cells. We have achieved efficient reprogramming by using SeVdp-Yamanaka factor gene system. To remove SeVdp vector gene from iPS cells after reprogramming, siRNA is discovered to have efficient vector removing activity. To investigate gene expression patterns during early process of the reprogramming, primordial germ cells (PGC) are employed to be induced to iPS cells. We found that several sequential steps of gene expression have occurred in process of iPS cells formation. To elucidate reprogramming steps, we developed direct RNA amplification methods without purification of RNA. We discovered a new type of human pluripotent stem cells, so-called “multilineage-differentiating stress enduring cell” (Muse cells). The Muse cells possess potential to differentiate into ectoderm, mesoderm, and entoderm. Since the muse cells are isolated without introduction of genes, they may not cause cancer development. We develop in vitro cardiotoxicity detection system using cardiomyocytes derived from stem cells such as human iPS cells. We have succeeded to produce human cardiomyocytes differentiated from various human stem cell sources such as normal skin- and blood T cell-derived iPS cells and also ES cells. Growth and differentiation conditions have been developed to supply suitable amount of cells for detection system. New improvement was done for the biochip design and detection system. Development of the total detection system advanced to be applicable for practical drug testing. Test drugs which have already known to induce QT prolongation and hERG psudo-positive and -negative in other systems are applied to the system. Comparative data are accumulating and used for further system improvement.
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