Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection.
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.
Genome Institute of Singapore, A-STAR, Singapore.
Pooja A
PA
Kumar
Yuanyu
Y
Hu
Yusuke
Y
Yamamoto
Neo Boon
NB
Hoe
Tay Seok
TS
Wei
Dakai
D
Mu
Yan
Y
Sun
Lim Siew
LS
Joo
Rania
R
Dagher
Elisabeth M
EM
Zielonka
De Yun
de Y
Wang
Bing
B
Lim
Vincent T
VT
Chow
Christopher P
CP
Crum
Wa
W
Xian
Frank
F
McKeon
D000818:Animals; D001980:Bronchi / Q000166:cytology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000473:pathology*; D008168:Lung / Q000166:cytology / Q000502:physiology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000821:virology; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics; D014945:Wound Healing
D014157:Transcription Factors