Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
Stem Cell Rev Rep. 2022 Dec;18(8):2629-2645. doi: 10.1007/s12015-022-10422-z. Epub 2022 Jul 23.
Several attempts have been made to reconstruct the whole lung using pluripotent stem cells (PSCs) to treat terminal stage diseases, such as chronic obstructive pulmonary disease [COPD] and idiopathic pulmonary fibrosis [IPF], for which whole-organ transplantation is currently the only treatment option. The development of induced differentiation technologies has made it possible to regenerate lungs from the 'bottom-up' via stepwise protocols. Nonetheless, the earliest lung multipotent progenitors, namely lung primordial stem cells, have not been identified to date. Considering the intricate crosstalk network that regulates lung development, stepwise protocols to differentiate PSCs into lung progenitors have raised some key questions: (1) the heterogeneity of these induced progenitors, and (2) obtaining a high-purity population. One important strategy to overcome these hurdles is to identify relevant markers or factors that regulate the complex network in lung morphogenesis according to those erected in vivo and ex vivo experiments. For screening lung primordial stem cells, several markers are 'on the shelf', and this review explores the most common or substantiated candidates. We artificially divided these markers into positive selecting and negative limiting proximal or distal markers as well as early progenitor markers that can be used to identify lung primordial stem cell, which represents the earliest progenitor during lung morphogenesis.
已经有几种尝试使用多能干细胞（PSCs）来重建整个肺，以治疗终末期疾病，如慢性阻塞性肺疾病[COPD]和特发性肺纤维化[IPF]，目前全器官移植是唯一的治疗选择。诱导分化技术的发展使得通过逐步方案从“底部向上”再生肺成为可能。尽管如此，迄今为止尚未鉴定出最早的肺多能祖细胞，即肺原始干细胞。考虑到调节肺发育的复杂串扰网络，将 PSCs 分化为肺祖细胞的逐步方案提出了一些关键问题：（1）这些诱导祖细胞的异质性，以及（2）获得高纯度群体。克服这些障碍的一个重要策略是根据体内和体外实验中建立的实验来鉴定调节肺形态发生中复杂网络的相关标记物或因子。为了筛选肺原始干细胞，已经有几种标记物“在货架上”，本综述探讨了最常见或最有根据的候选物。我们人为地将这些标记物分为阳性选择和阴性限制的近端或远端标记物以及早期祖细胞标记物，这些标记物可用于鉴定肺原始干细胞，它代表了肺形态发生过程中的最早祖细胞。
