Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease.
Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease.
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在肺稳态、组织再生和人类疾病中，气道上皮细胞的身份和可塑性受到Sox2的限制。
DOI：
10.1038/s41536-023-00344-w
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发表时间：
2024-01-05
影响因子：
7.2
通讯作者：
Morrisey, Edward E.
中科院分区：
文献类型：
--
作者：
Shiraishi, Kazushige;Morley, Michael P.;Jones, Dakota L.;Zhao, Gan;Weiner, Aaron I.;Basil, Maria C.;Cantu, Edward;Ferguson, Laura T.;Oyster, Michele;Babu, Apoorva;Ying, Yun;Zhou, Su;Li, Shanru;Vaughan, Andrew E.;Morrisey, Edward E.
维持气道和肺泡间室之间的细胞边界在稳态期间和损伤后是必不可少的，以防止可降低呼吸功能的病理性可塑性。肺损伤和疾病可诱导功能性肺泡上皮再生或角化上皮发育不良，而角化上皮不能有效地促进气体交换。在这里，我们发现Sox2保留了气道细胞的特性，并阻止肺损伤后肺泡组织或病理性角化的命运变化。气道上皮中Sox2的缺失导致气道上皮特征的丧失，肺泡和基底细胞特征相应增加，部分原因是分泌细胞中Wnt信号的激活和肺内基底样祖细胞中Trp63表达的增加。在特发性肺纤维化中，SOX2表达的缺失与发育不良的角化上皮中WNT信号活性的增加相关。在COVID-19受损的肺中也观察到sox2缺陷的发育不良上皮细胞。因此，Sox2提供了抑制气道上皮可塑性的分子屏障，以防止损伤后获得肺泡或基底细胞身份，并帮助指导上皮的正确命运和再生。
Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.
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影响因子：
7.7
作者：
Eenjes E;Buscop-van Kempen M;Boerema-de Munck A;Edel GG;Benthem F;de Kreij-de Bruin L;Schnater M;Tibboel D;Collins J;Rottier RJ
通讯作者：
Rottier RJ
DOI：
10.1083/jcb.200409182
发表时间：
2005-03-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mansukhani A;Ambrosetti D;Holmes G;Cornivelli L;Basilico C
通讯作者：
Basilico C
影响因子：
2.5
作者：
Kormish, Jay D.;Sinner, Debora;Zorn, Aaron M.
通讯作者：
Zorn, Aaron M.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Kim, CFB;Jackson, EL;Jacks, T
通讯作者：
Jacks, T