Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore.
PLoS One. 2013 Aug 5;8(8):e71028. doi: 10.1371/journal.pone.0071028. Print 2013.
Regeneration of alveolar epithelia following severe pulmonary damage is critical for lung function. We and others have previously shown that Scgb1a1-expressing cells, most likely Clara cells, can give rise to newly generated alveolar type 2 cells (AT2s) in response to severe lung damage induced by either influenza virus infection or bleomycin treatment. In this study, we have investigated cellular pathway underlying the Clara cell to AT2 differentiation. We show that the initial intermediates are bronchiolar epithelial cells that exhibit Clara cell morphology and express Clara cell marker, Scgb1a1, as well as the AT2 cell marker, pro-surfactant protein C (pro-SPC). These cells, referred to as pro-SPC(+) bronchiolar epithelial cells (or SBECs), gradually lose Scgb1a1 expression and give rise to pro-SPC(+) cells in the ring structures in the damaged parenchyma, which appear to differentiate into AT2s via a process sharing some features with that observed during alveolar epithelial development in the embryonic lung. These findings suggest that SBECs are intermediates of Clara cell to AT2 differentiation during the repair of alveolar epithelia following severe pulmonary injury.
肺泡上皮细胞在严重肺损伤后的再生对于肺功能至关重要。我们和其他人之前已经表明，Scgb1a1 表达细胞，很可能是 Clara 细胞，在流感病毒感染或博莱霉素处理引起的严重肺损伤后，可以产生新的肺泡 II 型细胞 (AT2)。在这项研究中，我们研究了 Clara 细胞向 AT2 分化的细胞途径。我们表明，最初的中间产物是细支气管上皮细胞，这些细胞表现出 Clara 细胞形态，并表达 Clara 细胞标志物 Scgb1a1 以及 AT2 细胞标志物 pro-表面活性剂蛋白 C (pro-SPC)。这些细胞被称为 pro-SPC(+)细支气管上皮细胞（或 SBEC），逐渐失去 Scgb1a1 表达，并在受损实质的环状结构中产生 pro-SPC(+)细胞，这些细胞似乎通过与胚胎肺中肺泡上皮发育过程中观察到的一些特征相似的过程分化为 AT2。这些发现表明，在严重肺损伤后肺泡上皮修复过程中，SBEC 是 Clara 细胞向 AT2 分化的中间产物。
