A novel subset of putative stem/progenitor CD34(+)Oct-4(+) cells is the major target for SARS coronavirus in human lung

Chen, Yongxiong; Chan, Vera Sau-Fong; Zheng, Bojian; Chan, Kelvin Yuen-Kwong; Xu, Xiaoning; To, Leo Yuk-Fai; Huang, Fang-Ping; Khoo, Ui-Soon; Lin, Chen-Lung Steve

Our current understanding about human lung stem/progenitor cells is limited. Recently, a subset of pulmonary Oct-4 Ï© stem/progenitor cells that could diff erentiate into pneumocytes has been isolated from neonatal mouse lung ( 14 ) . Of signifi cance, these mouse stem/progenitor cells express ACE2 and are susceptible to SARS-CoV infection and replication in vitro ( 14 ) , which at least in part supports our fi ndings. In the adult mouse lung, CD34 Ï© bronchioalveolar stem cells (BASCs) that can diff erentiate into alveolar epithelia have also been isolated ( 25 ) . The phenotype of the novel cell subset we identifi ed in the human lung, however, is not entirely compatible to those known mouse lung stem/progenitor cells. For example, the Oct-4 Ï© stem/progenitor cells isolated from the neonatal mouse lung express cytokeratin and CD15 (i.e., SSEA-1) ( 14 ), whereas our cells do not ( Fig. 3 ) . The BASCs identifi ed in the adult mouse lung express surfactant ( 25 ), which is undetectable in our cells. In addition, instead of being at the bronchioalveolar duct junction where the BASCs are located ( 25 ), our cells are scattered in the lung stroma ( Fig. 3 A ) and in the bronchiolar lining layer (Fig. S6) . Nevertheless, we notice that some CD34 Ï© Oct4 Ï© cells in the non-SARS lung are actually juxtaposed to the cytokeratin Ï© or surfactant Ï© cells ( Fig. 3 A ) . Therefore, the possibility that these putative stem/progenitor cells in the human lung may diff erentiate into mature respiratory epithelia or pneumocytes, as in the case in mice, cannot be excluded.