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c-kit+ cells adopt vascular endothelial but not epithelial cell fates during lung maintenance and repair

Abstract

Unraveling the fate specification of resident stem cells during lung regeneration is of clinical importance. It has been reported that c-kit+ progenitor cells resident in the human lung regenerate epithelial lineages upon transplantation into injured mouse lung. Here we test the lineage potential of c-kit+ cells by inducible genetic lineage tracing. We find that c-kit+ cells do not contribute to lung epithelium during homeostasis and repair, and instead maintain a vascular endothelial cell fate. These findings call attention to the clinical application of c-kit+ stem cells as lung epithelial progenitors for the treatment of pulmonary disease.

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Figure 1: Upon cryoinjury, c-kit+ cells do not generate lung epithelium.
Figure 2: Upon pneumonectomy, c-kit+ cells do not contribute to lung epithelium.

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Acknowledgements

We thank H. Zeng from the Allen Institute for Brain Science for providing Ai9 and Ai47 mouse lines. We thank Shanghai Biomodel Organism Co., Ltd. for generating Kit-CreER mouse line. This work was supported by the National Science Foundation of China (91339104, 31271552, 31222038 to B.Z.; 31301188 to X.T.), the Ministry of Science and Technology (2012CB945102, 2013CB945302 to B.Z.), the Bajian Talent Project (B.Z.), the Shanghai Basic Research Key Project (14JC1407400 to B.Z.), the Shanghai Institutes for Biological Sciences (SIBS) President Fund (B.Z.), a Sanofi-SIBS Fellowship (X.T.), AstraZeneca, Shanghai Yangfan Project grant (15YF1414000 to H.Z.) and by a Qimingxing Project grant (15QA1404300 to X.T.).

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Q.L. conducted experiments and analyzed the data. X.H., H.Z., X.T., L.H., R.Y., Y.Y. and Q.-D.W. bred mice, performed experiments or provided discussion. A.G. provided valuable suggestions and comments, interpreted data and edited the manuscript. B.Z. supervised the study, interpreted the data and wrote the manuscript.

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Correspondence to Bin Zhou.

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The authors declare no competing financial interests.

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Liu, Q., Huang, X., Zhang, H. et al. c-kit+ cells adopt vascular endothelial but not epithelial cell fates during lung maintenance and repair. Nat Med 21, 866–868 (2015). https://doi.org/10.1038/nm.3888

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