Identification of pulmonary Oct-4 ⁺ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro

Abstract

In this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamerbinding transcription factor 4 ؉ (Oct-4 ؉ ) epithelial colonies with a surrounding mesenchymal stroma. In addition to Oct-4, these cells also express other stem cell markers such as stage-specific embryonic antigen 1 (SSEA-1), stem cell antigen 1 (Sca-1), and Clara cell secretion protein (CCSP) but not c-Kit, CD34, and p63, indicating that they represent a subpopulation of Clara cells that have been implicated as lung stem͞progenitor cells in lung injury models. These colony cells can be kept for weeks in primary cultures and undergo terminal differentiation to alveolar type-2-and type-1-like pneumocytes sequentially when removed from the stroma.

Identification and expansion of the tumorigenic lung cancer stem cell population

“…28 Although there is not a full overlap between human and mouse stem cell antigens, human lung cancer CD133 þ cells and mouse bronchoalveolar stem cells share to some extent the expression of the stem cell markers CD34, BCRP1, Oct4 and the absence of pan-hematopoietic (CD45) and -endothelial (CD31) antigens. 16,24 Moreover, we observed that the rare CD133 þ cells present in the mouse lung increase considerably following naphthalene-induced injury, in line with the possibility that CD133 may be expressed in mouse bronchoalveolar stem cells. In contrast, the bronchoalveolar stem cell and alveolar type 2 cell marker SP-C showed a variable expression in lung cancer spheres, reflecting the phenotypic variability of human lung cancer stem cells.…”

Bone marrow‐derived very small embryonic‐like stem cells: Their developmental origin and biological significance

“…A population of stem cells that express markers of ESC/epiblast/PGC cells was recently described in several nonhematopoietic organs, for example, in epidermis (Dyce et al, 2004(Dyce et al, , 2006Yu et al, 2006), bronchial epithelium (Ling et al, 2006), myocardium, pancreas, (Kruse et al, 2006;Danner et al, 2007), testis (Kanatsu-Shinohara et al, 2004;Guan et al, 2006), retina (Koso et al, 2006), and amniotic fluid (De Coppi et al, 2007). This finding supports a concept of developmental deposition of Oct-4 ϩ EPSC in developing organs.…”

Effects of estrogen on the proportion of stem cells in the breast

“…The regulatory networks controlling the function of ES cells, including key regulators of ES cell maintenance, namely Nanog, Oct4 and Sox2 [16,17], are also found in some adult stem cell populations [18,19]. Moreover, genes associated with ES cell identity have been linked to tumor histology, supporting the possibility that these genes contribute to the stem cell-like phenotype of many tumors [20].…”