Rare SOX2(+) Airway Progenitor Cells Generate KRT5(+) Cells that Repopulate Damaged Alveolar Parenchyma following Influenza Virus Infection.
Rare SOX2(+) Airway Progenitor Cells Generate KRT5(+) Cells that Repopulate Damaged Alveolar Parenchyma following Influenza Virus Infection.
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DOI：
10.1016/j.stemcr.2016.09.010
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发表时间：
2016-11-08
影响因子：
5.9
通讯作者：
Stripp, Barry R.
中科院分区：
文献类型：
--
作者：
Ray, Samriddha;Chiba, Norika;Yao, Changfu;Guan, Xiangrong;McConnell, Alicia M.;Brockway, Brian;Que, Loretta;McQualter, Jonathan L.;Stripp, Barry R.
最近的研究表明角蛋白 5 (KRT5)+ 细胞参与严重 H1N1 流感病毒感染后受损肺组织的重新增殖。然而，重新填充受损肺泡区域的细胞的起源仍然存在争议。我们试图确定流感感染后肺修复的细胞动力学，并确定重新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 KRT5+ 细胞，作为对气道损伤的早期反应，并产生在受损肺泡实质中定植的后代。此外，我们发现局部肺泡祖细胞在损伤后对新生 KRT5+ 细胞没有贡献。受损气道和肺泡区域的重建导致假复层上皮使远端气道近端化，以及缺乏成熟气道或肺泡上皮正常特征的气道来源上皮细胞使肺泡近端化。流感诱导重塑的远端肺上皮中出现 KRT5+ 细胞 肺泡祖细胞对新生 KRT5+ 细胞没有贡献 多个气道祖细胞在气道中产生新生 KRT5+ 细胞 SOX2 谱系标记的细胞是新生 KRT5+ 细胞的主要细胞来源 Stripp 及其同事报告说，小鼠体内 H1N1 流感病毒感染可诱导远端肺上皮重塑，其特征是出现受损气道和肺泡中的新生 KRT5+ 细胞。他们追踪这些新生 KRT5+ 细胞的细胞起源，而不是预先存在的基底、俱乐部和肺泡祖细胞，而是一群气道驻留的 SOX2+ Lin− 祖细胞。
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. Influenza induces KRT5+ cell appearance in remodeled distal lung epithelium Alveolar progenitor cells do not contribute to nascent KRT5+ cells Multiple airway progenitor cells give rise to nascent KRT5+ cells in airways SOX2 lineage-labeled cells are the major cellular source of nascent KRT5+ cells Stripp and colleagues report that H1N1 influenza virus infection in mice induces distal lung epithelial remodeling marked by the appearance of nascent KRT5+ cells in injured airways and alveoli. Rather than pre-existing basal, club, and alveolar progenitor cells, they traced the cellular origin of these nascent KRT5+ cells to a population of airway-resident SOX2+ Lin− progenitor cells.
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影响因子：
64.5
作者：
Kumar PA;Hu Y;Yamamoto Y;Hoe NB;Wei TS;Mu D;Sun Y;Joo LS;Dagher R;Zielonka EM;Wang de Y;Lim B;Chow VT;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
谱系阴性祖细胞大受伤后动员肺上皮。
影响因子：
64.8
作者：
Vaughan, Andrew E.;Brumwell, Alexis N.;Xi, Ying;Gotts, Jeffrey E.;Brownfield, Doug G.;Treutlein, Barbara;Tan, Kevin;Tan, Victor;Liu, Feng Chun;Looney, Mark R.;Matthay, Michael A.;Rock, Jason R.;Chapman, Harold A.
通讯作者：
Chapman, Harold A.
影响因子：
16.6
作者：
Jain, Rajan;Barkauskas, Christina E.;Takeda, Norifumi;Bowie, Emily J.;Aghajanian, Haig;Wang, Qiaohong;Padmanabhan, Arun;Manderfield, Lauren J.;Gupta, Mudit;Li, Deqiang;Li, Li;Trivedi, Chinmay M.;Hogan, Brigid L. M.;Epstein, Jonathan A.
通讯作者：
Epstein, Jonathan A.
p63（+）KRT5（+）远端气道干细胞对于肺部再生至关重要。
影响因子：
64.8
作者：
Zuo W;Zhang T;Wu DZ;Guan SP;Liew AA;Yamamoto Y;Wang X;Lim SJ;Vincent M;Lessard M;Crum CP;Xian W;McKeon F
通讯作者：
McKeon F
影响因子：
15.9
作者：
Chapman, Harold A.;Li, Xiaopeng;Vu, Thiennu H.
通讯作者：
Vu, Thiennu H.