Distal Airway Stem Cells Yield Alveoli In Vitro and during Lung Regeneration following H1N1 Influenza Infection

被引：447

作者：

Kumar, Pooja A. ^{[1
,2
]}

Hu, Yuanyu ^{[1
]}

Yamamoto, Yusuke ^{[1
]}

Hoe, Neo Boon ^{[1
]}

Wei, Tay Seok ^{[1
,3
]}

Mu, Dakai ^{[4
]}

Sun, Yan ^{[4
]}

Joo, Lim Siew ^{[1
]}

Dagher, Rania ^{[5
]}

Zielonka, Elisabeth M. ^{[5
]}

Wang, De Yun ^{[6
]}

Lim, Bing ^{[1
]}

Chow, Vincent T. ^{[7
]}

Crum, Christopher P. ^{[8
]}

Xian, Wa ^{[3
,8
]}

McKeon, Frank ^{[1
,4
]}

机构：

[1] ASTAR, Genome Inst Singapore, Singapore, Singapore

[2] Natl Univ Singapore, Singapore Massachusetts Inst Technol Alliance, Singapore 117548, Singapore

[3] ASTAR, Inst Med Biol, Singapore, Singapore

[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA

[5] Univ Strasbourg, Inst Sci & Ingn Supramol, Strasbourg, France

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Otolaryngol, Singapore 117595, Singapore

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Infect Dis Program, Dept Microbiol, Singapore 117595, Singapore

[8] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

CELL | 2011年 / 147卷 / 03期

基金：

欧洲研究理事会;

关键词：

RESPIRATORY-DISTRESS-SYNDROME; MOUSE MODEL; EPITHELIUM; VIRUS; MICE; REPAIR; P63; MAINTENANCE; HOMEOSTASIS; ANTIBODY;

D O I：

10.1016/j.cell.2011.10.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：525 / 538

页数：14

共 39 条

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