<博士論文>
ダイレクトリプログラミングによるオルガノイド形成能を有するマウスおよびヒト腸前駆細胞の作製

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概要 Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent... stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties. The resulting stem cells produce all intestinal epithelial cell lineages and undergo self-renewing cell divisions. After transplantation, the induced spherical and budding organoids can reconstitute colonic and intestinal epithelia, respectively. The same combination of four defined transcription factors can also induce human iFIPCs. This alternative approach for producing intestinal organoids may well facilitate application for disease analysis and therapy development.続きを見る

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pdf med3104_abstract pdf 168 KB 284 要旨
pdf med3104_summary pdf 168 KB 139 要約
pdf med3104_review pdf 176 KB 153 審査結果要旨

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登録日 2018.05.30
更新日 2018.08.31

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