Alveolar progenitor and stem cells in lung development, renewal and cancer.
Alveolar progenitor and stem cells in lung development, renewal and cancer.
复制标题
肺发育、更新和癌症中的肺泡祖细胞和干细胞。
作者：
Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing, and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that during development AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGF ligands in vitro and oncogenic KrasG12D in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair, and cancer. We propose that local signals regulate AT2 stem cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, while another signal controls reprogramming to AT1 fate.
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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
影响因子：
64.5
作者：
Kretzschmar, Kai;Watt, Fiona M.
通讯作者：
Watt, Fiona M.
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
3.7
作者：
Lin C;Song H;Huang C;Yao E;Gacayan R;Xu SM;Chuang PT
通讯作者：
Chuang PT
影响因子：
15.9
作者：
Chapman, Harold A.;Li, Xiaopeng;Vu, Thiennu H.
通讯作者：
Vu, Thiennu H.