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Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection |
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| Authors: | Kumar Pooja A Hu Yuanyu Yamamoto Yusuke Hoe Neo Boon Wei Tay Seok Mu Dakai Sun Yan Joo Lim Siew Dagher Rania Zielonka Elisabeth M Wang De Yun Lim Bing Chow Vincent T Crum Christopher P Xian Wa McKeon Frank |
| Institution: | 1 Genome Institute of Singapore, A-STAR, Singapore 2 Computation and Systems Biology, Singapore-Massachusetts Institute of Technology Alliance, National University of Singapore, Singapore 3 Institute of Medical Biology, A-STAR, Singapore 4 Department of Cell Biology, Harvard Medical School, Boston, MA, USA 5 Institut de Science et d'Ingénierie Supramoléculaires, University of Strasbourg, Strasbourg, France 6 Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore 7 Infectious Diseases Program, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 8 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA |
| Abstract: | The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. |
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