Multiple adult tissues are maintained by stem cells of restricted developmental potential which can only form a subset of lineages within the tissue. For instance, the two adult lung epithelial compartments (airways and alveoli) are separately maintained by distinct lineage-restricted stem cells. A challenge has been to obtain multipotent stem cells and/or progenitors that can generate all epithelial cell types of a given tissue. Here we show that mouse Sox9+ multipotent embryonic lung progenitors can be isolated and expanded long term in 3D culture. Cultured Sox9+ progenitors transcriptionally resemble their in vivo counterparts and generate both airway and alveolar cell types in vitro. Sox9+ progenitors that were transplanted into injured adult mouse lungs differentiated into all major airway and alveolar lineages in vivo in a region-appropriate fashion. We propose that a single expandable embryonic lung progenitor population with broader developmental competence may eventually be used as an alternative for region-restricted adult tissue stem cells in regenerative medicine.

中文翻译：

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多能Sox9 +小鼠肺祖细胞的分离和3D扩增。

发育潜力有限的干细胞可维持多个成年组织，这些干细胞只能在组织内形成谱系的子集。例如，两个成年的肺上皮区室（气道和肺泡）由不同的谱系限制干细胞分别维持。获得可产生给定组织的所有上皮细胞类型的多能干细胞和/或祖细胞一直是一个挑战。在这里，我们显示可以在3D文化中长期分离和扩展小鼠Sox9 +多能胚胎肺祖细胞。培养的Sox9 +祖细胞在转录上类似于它们的体内对应物，并在体外产生气道和肺泡细胞类型。移植到受损成年小鼠肺中的Sox9 +祖细胞以适合区域的方式在体内分化为所有主要气道和肺泡谱系。我们建议，具有更广泛的开发能力的单个可扩展的胚胎肺祖细胞最终可以在再生医学中用作区域受限的成人组织干细胞的替代方法。