Ray Samriddha, Chiba Norika, Yao Changfu, Guan Xiangrong, McConnell Alicia M, Brockway Brian, Que Loretta, McQualter Jonathan L, Stripp Barry R
Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Lung and Regenerative Medicine Institutes, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Stem Cell Reports. 2016 Nov 8;7(5):817-825. doi: 10.1016/j.stemcr.2016.09.010. Epub 2016 Oct 20.
Recent studies have implicated keratin 5 (KRT5) cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5 cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells. We found that the wound-healing response begins with proliferation of SOX2 SCGB1A1 KRT5 progenitor cells in airways. These cells generate nascent KRT5 cells as an early response to airway injury and yield progeny that colonize damaged alveolar parenchyma. Moreover, we show that local alveolar progenitors do not contribute to nascent KRT5 cells after injury. Repopulation of injured airway and alveolar regions leads to proximalization of distal airways by pseudostratified epithelium and of alveoli by airway-derived epithelial cells that lack the normal characteristics of mature airway or alveolar epithelium.
最近的研究表明，在严重的H1N1流感病毒感染后，角蛋白5（KRT5）细胞参与了受损肺组织的再填充。然而，再填充受损肺泡区域的细胞来源仍存在争议。我们试图确定流感感染后肺修复的细胞动力学，并确定再填充肺泡上皮的新生KRT5细胞是否源自预先存在的肺泡或气道祖细胞。我们发现，伤口愈合反应始于气道中SOX2 SCGB1A1 KRT5祖细胞的增殖。这些细胞产生新生的KRT5细胞作为对气道损伤的早期反应，并产生定殖于受损肺泡实质的子代细胞。此外，我们表明，局部肺泡祖细胞在损伤后不会产生新生的KRT5细胞。受损气道和肺泡区域的再填充导致远端气道被假复层上皮近端化，肺泡被缺乏成熟气道或肺泡上皮正常特征的气道衍生上皮细胞近端化。
