School of Veterinary Medicine, Department of Biomedical Sciences, The University of Pennsylvania, 3800 Spruce Street, Philadelphia, USA; Institute for Regenerative Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, USA.
School of Veterinary Medicine, Department of Biomedical Sciences, The University of Pennsylvania, 3800 Spruce Street, Philadelphia, USA; Perelman School of Medicine, The University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, USA; Institute for Regenerative Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, USA.
Stem Cell Reports. 2020 Nov 10;15(5):1015-1025. doi: 10.1016/j.stemcr.2020.09.006. Epub 2020 Oct 15.
Despite the central importance of the respiratory system, the exact mechanisms governing lung repair after severe injury remain unclear. The notion that alveolar type 2 cells (AT2s) self-renew and differentiate into alveolar type 1 cells (AT1s) does not fully encompass scenarios where these progenitors are severely affected by disease, e.g., H1N1 influenza or SARS-CoV-2 (COVID-19). Intrapulmonary p63 progenitor cells, a rare cell type in mice but potentially encompassing more numerous classic basal cells in humans, are activated in such severe injury settings, proliferating and migrating into the injured alveolar parenchyma, providing a short-term "emergency" benefit. While the fate of these cells is controversial, most studies indicate that they represent a maladaptive repair pathway with a fate restriction toward airway cell types, rarely differentiating into AT2 or AT1 cells. Here, we discuss the role of intrapulmonary basal-like p63 cells in alveolar regeneration and suggest a unified model to guide future studies.
尽管呼吸系统至关重要，但严重损伤后肺部修复的确切机制仍不清楚。肺泡 II 型细胞 (AT2) 自我更新并分化为肺泡 I 型细胞 (AT1) 的观点并不能完全涵盖这些祖细胞因疾病而严重受损的情况，例如 H1N1 流感或 SARS-CoV-2（COVID-19）。肺内 p63 祖细胞是一种在小鼠中罕见但在人类中可能包含更多经典基底细胞的细胞类型，在这种严重损伤的情况下被激活，增殖并迁移到受损的肺泡实质中，提供短期的“应急”益处。虽然这些细胞的命运存在争议，但大多数研究表明，它们代表一种适应不良的修复途径，其命运限制在气道细胞类型上，很少分化为 AT2 或 AT1 细胞。在这里，我们讨论了肺内基底样 p63 细胞在肺泡再生中的作用，并提出了一个统一的模型来指导未来的研究。
