Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids.
Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids.
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DOI：
10.1016/j.stemcr.2018.01.006
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发表时间：
2018-03-13
影响因子：
5.9
通讯作者：
Taniguchi H
中科院分区：
文献类型：
--
作者：
Zhang RR;Koido M;Tadokoro T;Ouchi R;Matsuno T;Ueno Y;Sekine K;Takebe T;Taniguchi H
早期内胚层祖细胞天然地具有强大的繁殖潜力以发育大多数米长的胃肠道，因此被认为是有希望的治疗来源。在这里，我们证明了人CDX 2+后肠内胚层细胞（PGECs）的可重复的生产从五个诱导多能干细胞克隆通过操纵FGF，TGF，和WNT信号。转录组分析表明，假定PGEC窝藏中间签名档案之间的定形内胚层和器官特异性内胚层。我们发现，组合EGF、VEGF、FGF 2、Chir 99021和A83-01处理选择性扩增可储存PGEC高达1021个细胞规模，而无需任何基因转导或饲养层使用。与诱导多能干细胞相比，PGECs表现出稳定的向多种内胚层谱系分化的倾向，而不形成畸胎瘤。此外，移植PGEC衍生的肝芽类器官显示出对暴发性肝衰竭的治疗潜力。总之，稳健扩增的PGEC可能是研究人类发育，疾病建模以及最终治疗中内胚层衍生类器官的有前途的细胞来源。使用人iPSC衍生的内胚层CDX 2 + PGEC的后分化程序的成功激活在传代和冷冻具有分化成后肠和肝芽类器官潜能的PGEC后表现出稳健的扩增潜能PGEC肝芽移植对急性肝衰竭是治疗有效的。和同事从人类多能干细胞中衍生出独特的CDX 2+后内胚层祖细胞（PGEC）群体，所述多能干细胞在化学限定的条件下高度可扩增和可储存。CDX 2+内胚层祖细胞可以形成多个内胚层类器官。从健壮繁殖的PGECs移植人肝芽类器官拯救了免疫缺陷小鼠的致死性肝功能衰竭。
Early endoderm progenitors naturally possess robust propagating potential to develop a majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF, and WNT signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm. We found that combinatorial EGF, VEGF, FGF2, Chir99021, and A83-01 treatments selectively amplify storable PGECs up to 1021 cell scale without any gene transduction or feeder use. PGECs, compared with induced pluripotent stem cells, showed stable differentiation propensity into multiple endodermal lineages without teratoma formation. Furthermore, transplantation of PGEC-derived liver bud organoids showed therapeutic potential against fulminant liver failure. Together, the robustly amplified PGECs may be a promising cellular source for endoderm-derived organoids in studying human development, modeling disease, and, ultimately, therapy. Successful activation of posteriorization program using human iPSC-derived endoderm CDX2+ PGECs exhibit a robust amplification potential after passaging and freezing PGECs with differentiation potential into hindgut and liver bud organoids PGEC liver bud transplant is therapeutically effective for acute liver failure In this article, Takebe, Taniguchi, and colleagues derived a unique population of CDX2+ posterior endoderm progenitors (PGECs) from human pluripotent stem cells that are highly expandable and storable in a chemically defined condition. CDX2+ endoderm progenitors can form multiple endodermal organoids. Transplantation of human liver bud organoids from robustly propagated PGECs rescued lethal liver failure of immunodeficient mice.
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影响因子：
7.2
作者：
Sheaffer KL;Kaestner KH
通讯作者：
Kaestner KH
影响因子：
24.5
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作者：
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通讯作者：
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作者：
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通讯作者：
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