In Vitro Induction and In Vivo Engraftment of Lung Bud Tip Progenitor Cells Derived from Human Pluripotent Stem Cells.
In Vitro Induction and In Vivo Engraftment of Lung Bud Tip Progenitor Cells Derived from Human Pluripotent Stem Cells.
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DOI：
10.1016/j.stemcr.2017.11.012
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发表时间：
2018-01-09
影响因子：
5.9
通讯作者：
Spence JR
中科院分区：
文献类型：
--
作者：
Miller AJ;Hill DR;Nagy MS;Aoki Y;Dye BR;Chin AM;Huang S;Zhu F;White ES;Lama V;Spence JR
目前的研究旨在了解调节人胎肺中芽尖祖细胞的发育机制，这些细胞存在于分支形态发生过程中，并利用这些信息在体外从人多能干细胞（hPSC）诱导芽尖祖细胞样群体。我们确定了在体外维持分离的人胎肺上皮芽尖祖细胞并诱导具有芽尖样结构域的三维hPSC衍生类器官的线索。芽尖样域可以被隔离，扩大，并保持作为一个几乎同质的人口。分子和细胞比较显示，hPSC衍生的芽尖样细胞与天然肺芽尖祖细胞高度相似。hPSC衍生的上皮芽尖样结构在体外存活超过16周，可以容易地冷冻和解冻，保持多谱系潜力，并成功地移植到免疫受损小鼠肺的气道中，在那里它们持续长达6周并产生几种肺上皮谱系。Fgf 7、CHIR-99021和RA支持人肺芽尖祖细胞的体外生长这些因子在体外从hPSC诱导肺芽尖祖细胞样类器官hPSC衍生的类器官与人胎儿芽尖祖细胞hPSC衍生的芽尖类器官高度相似移植到损伤的小鼠气道中在这篇文章中，Jason Spence及其同事确定了一个核心信号网络，该网络在体外维持分离的人上皮肺芽尖祖细胞，并从hPSC诱导芽尖样群体。他们表明，iPSC衍生的芽尖祖细胞可以移植到受损的小鼠气道中，有助于上皮再形成，并分化成多种肺上皮谱系。
The current study aimed to understand the developmental mechanisms regulating bud tip progenitor cells in the human fetal lung, which are present during branching morphogenesis, and to use this information to induce a bud tip progenitor-like population from human pluripotent stem cells (hPSCs) in vitro. We identified cues that maintained isolated human fetal lung epithelial bud tip progenitor cells in vitro and induced three-dimensional hPSC-derived organoids with bud tip-like domains. Bud tip-like domains could be isolated, expanded, and maintained as a nearly homogeneous population. Molecular and cellular comparisons revealed that hPSC-derived bud tip-like cells are highly similar to native lung bud tip progenitors. hPSC-derived epithelial bud tip-like structures survived in vitro for over 16 weeks, could be easily frozen and thawed, maintained multilineage potential, and successfully engrafted into the airways of immunocompromised mouse lungs, where they persisted for up to 6 weeks and gave rise to several lung epithelial lineages. Fgf7, CHIR-99021, and RA support growth of human lung bud tip progenitors in vitro These factors induce lung bud tip progenitor-like organoids from hPSCs in vitro hPSC-derived organoids are highly similar to human fetal bud tip progenitors hPSC-derived bud tip organoids engraft into the injured murine airway In this article, Jason Spence and colleagues identify a core signaling network that maintains isolated human epithelial lung bud tip progenitors in vitro and that induces a bud tip-like population from hPSCs. They show that iPSC-derived bud tip progenitors can engraft into an injured mouse airway, contribute to re-epithelialization, and differentiate into multiple lung epithelial lineages.
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影响因子：
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影响因子：
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作者：
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Snoeck HW
影响因子：
23.9
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作者：
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通讯作者：
Spence JR