Stable iPSC-derived NKX2-1+ lung bud tip progenitor organoids give rise to airway and alveolar cell types.
Stable iPSC-derived NKX2-1+ lung bud tip progenitor organoids give rise to airway and alveolar cell types.
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DOI：
10.1242/dev.200693
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发表时间：
2022-10-15
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影响因子：
--
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发育中的肺中的芽尖祖细胞（BTP）产生在气道和肺泡中发现的所有上皮细胞类型。这项工作旨在开发富含NKX2 - 1 + BTP样细胞的iPSC类器官模型。基于先前的研究，我们优化了定向分化范式以产生具有更稳健的NKX2 - 1表达的球状体。将球状体扩增成具有NKX2 - 1 +/CPM + BTP样细胞的类器官，其数量随时间增加。单细胞RNA测序分析揭示了诱导的BTP（iBTP）和体内BTP之间的高度转录相似性。使用FACS，将iBTP纯化并扩增为诱导的芽尖祖细胞类器官（iBTO），其维持芽尖祖细胞的富集群体。当使用成熟的方法引导iBTO分化成气道或肺泡细胞类型时，它们分别产生由组织化气道或肺泡上皮组成的类器官。总的来说，iBTO在转录和功能上与体内BTP相似，为研究人类肺发育和分化提供了重要模型。总结：iPSC衍生的肺芽尖祖细胞出现在类器官培养物中，可以分离和扩增，在转录上类似于初级芽尖祖细胞，并且可以分化成气道或肺泡类器官。
Bud tip progenitors (BTPs) in the developing lung give rise to all epithelial cell types found in the airways and alveoli. This work aimed to develop an iPSC organoid model enriched with NKX2-1+ BTP-like cells. Building on previous studies, we optimized a directed differentiation paradigm to generate spheroids with more robust NKX2-1 expression. Spheroids were expanded into organoids that possessed NKX2-1+/CPM+ BTP-like cells, which increased in number over time. Single cell RNA-sequencing analysis revealed a high degree of transcriptional similarity between induced BTPs (iBTPs) and in vivo BTPs. Using FACS, iBTPs were purified and expanded as induced bud tip progenitor organoids (iBTOs), which maintained an enriched population of bud tip progenitors. When iBTOs were directed to differentiate into airway or alveolar cell types using well-established methods, they gave rise to organoids composed of organized airway or alveolar epithelium, respectively. Collectively, iBTOs are transcriptionally and functionally similar to in vivo BTPs, providing an important model for studying human lung development and differentiation. Summary: iPSC-derived lung bud tip progenitors emerge in organoid culture, can be isolated and expanded, are transcriptionally similar to primary bud tip progenitors, and can differentiate into airway or alveolar organoids.
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影响因子：
46.9
作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.0902274106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Harris-Johnson, Kelley S.;Domyan, Eric T.;Sun, Xin
通讯作者：
Sun, Xin