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

Because SARS Ï© cells did not express cytokeratin or surfactant A ( Fig. 1 ), we investigated if the SARS Ï© cells might be (a -c) IHC on SARS autopsy lung for CD68 (brown labeling, some indicated by dark blue arrows in a) and for SARS-CoV antigen (red labeling, some indicated by red arrows in a; also visible in b and c), followed by FISH for ACE2 (green labeling in b, some indicated by green arrows and a circle) and ISH for CD34 (purple labeling in c, some indicated by light blue arrows and a circle). Circles in a, b, and c indicate uninfected ACE2 Ï© CD34 Ï© cells. (e -g) Isotype antibody control for IHC, ACE2 sense control for FISH, and CD34 sense control for ISH, respectively. (i -k) IHC for SARS-CoV antigen (red labeling, some indicated by red arrows in i; also visible in j and k), followed by FISH for CD34 (green labeling in j, some indicated by light blue arrows and circles), and ISH for Oct-4 (purple labeling in k, some indicated by purple arrows and circles). Circles in j and k indicate uninfected CD34 Ï© Oct-4 Ï© cells. Isotype antibody control for IHC, CD34 sense control for FISH, and Oct-4 sense control for ISH are similar to e, f, and g, respectively (not depicted). DAPI counterstaining is in the right column. Panels of each row represent results on the same section of a patient. Results are representative of six SARS patients. Bar, 20 m. express ACE2 but not cytokeratin; however, only the latter contain SARS-CoV antigen in the SARS lung. We also note that the frequency of CD34 Ï© cells in the non-SARS lung appears to be higher than that of SARS Ï© cells in the SARS samples. However, these numbers cannot be directly compared because the non-SARS lung samples were from lung cancer patients, which may not represent the situations in healthy individuals who have no lung pathology. Furthermore, it is still unclear how the frequency of these putative stem/progenitor cells is regulated, for example, in cancers.