We have recently identified a rare subpopulation of lung cells (0.004%) with the characteristics of pulmonary stem /progenitor cells, which appear to interact with their surrounding mesenchymal stroma cells to maintain their phenotypes as stem cells. These pulmonary stem /progenitor cells represent a population of slow cycling, Oct-4 expressing cells scattered at bronchoalveolar junctions of lung tissues. They formed individual colonies in in vitro cultures and expressed stem cell specific antigens as well as some markers of epithelial and Clara cell lineages. These morphologically unique colony cells can be kept in primary cultures for months and undergo terminal differentiation to alveolar type-2 and type-1 pneumocytes sequentially when removed from the stroma. We have also demonstrated that these adult lung stem cells may play a key role in the SARS epidemics. This study shows the lung stem cells, while not easily spotted, was an important target of SARS viruses in lung tissues. The discovery has implicated a possible involvement of lung stem cells in SARS-CoV infection, accounting for the continued deterioration of lung tissues and apparent loss of capacity for lung repair in the later stage of infection.

We had been working on the study of the molecular mechanism of growth factors [e.g. transforming growth factors (TGF- b s), platelet derived growth factor (PDGF), insulin-like growth factor (IGF)] and its modulators [e.g. a -2 macroglobulin (A2M), insulin-like growth factor binding proteins (IGFBPs)] for murine embryonic fibroblast and epithelium cells. In our study, a 600-kDa TGF- b receptor was purified from plasma membrane of bovine liver and proved to be one member of LDL receptor family. The receptor was detected by cross-linking assay and identified by 2D-PAGE, MALDI-TOF and protein sequencing. The receptor was a multiple ligands (e.g. IGFBP3, TGF- b ) receptor with Ser/Thr-specific protein kinase activity. We had also evaluated the activity of TGF- b and the synthetic TGF- b pentacosapeptide antagonist was used. This antagonist could block TGF- b activity and have therapeutic utility that accelerated wound healing and reduces scarring. The activity of TGF- b in plasma could be regulating by A2M by forming TGF- b- A2M complex. In our study, we had demonstrated that fatty acid could modulate the TGF- b- A2M complex in order to increase plasma clearance of TGF- b in blood .

近期代表著作：

1] Lung-derived SSEA-1+ stem/progenitor cells inhibit allergic airway inflammation in mice.  Allergy. 2015 Jan 6. doi: 10.1111/all.12567.  [Abstract]

2] Activation of IL6/IGFIR Confers Poor Prognosis of HBV-Related Hepatocellular Carcinoma through Induction of OCT4/NANOG Expression. Clin Cancer Res. 2015 Jan 1;21(1):201-10.  [Abstract]

3] Hypoxia inducible factor 2α/insulin-like growth factor receptor signal loop supports the proliferation and Oct-4maintenance of mouse germline stem cells. Mol Hum Reprod. 2014 Jun;20(6):526-37.   [Abstract]

4] Differentiation of lung stem/progenitor cells into alveolar pneumocytes and induction of angiogenesis within a 3D gelatin--microbubble scaffold. Biomaterials. 2014 Jul;35(22):5660-9.  [Abstract]

5] Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Nat Commun. 2014 Mar 25;5:3472.   [Abstract]

6] Enhancement role of host 12/15-lipoxygenase in melanoma progression. Eur J Cancer. 2013 Aug;49(12):2747-59.   [Abstract]

7] FGF-9 accelerates epithelial invagination for ectodermal organogenesis in real time bioengineered organ manipulation. Cell Commun Signal. 2012 Nov 23;10(1):34.   [Abstract]

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Our studies will use the pulmonary stem/progenitor cells for lung injury in animal model by transplantation and try to establish the culture system to identify other stem/progenitor cell population in different tissues and different species. The studies will also focus on the mechanism between mesenchymal-epithelial interactions by exogenous stem/progenitor cells from the circulation or transplantation versus those that activate endogenous cells with regenerative capacity in tissues development and repair.

1] PCR

2] Cell culture