Evidence for stem/progenitor cells in mouse lung model

I came across this excellent paper and summarized my "top 10 list" of points from the paper.  The role of stem/progenitor cells in cancer is a crazy-active area in current research.  If you catch some of the details, you can probably guess the technical challenges to this work.

 

Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung

Jonathan L. McQualtera, Karen Yuena, Brenda Williams, and Ivan Bertoncello

PNAS 2010; 107:1414-1419.

1. Mesenchymal progenitor cells (EpCAM^neg Sca-1^pos) regulate the growth of EpCAM^pos lung progenitor/stem cells in in vitro matrigel cultures.
2. Fibroblast growth factor-10 and hepatocyte growth factor regulate epithelial cfus even in stromal-free cultures and appear to act synergistically, while the addition of mesenchymal growth factors [bone morphogenic protein (BMP-4), TGF-beta1, or platelet-derived growth factor (PDGF)-AA] resulted in a significant reduction or complete inhibition of epithelial colony growth.
3. Lung epithelial cells comprise less than 0.05% of lung epithelial cells and are predominantly restricted to the EpCAM^hi CD49f^pos (α-6-integrin) cell fraction.
4. The EpCAM^hi cell fraction was exclusively CD104^pos (β-4 integrin).
5. In the adult mouse lung, immunofluorescent staining demonstrated that CD104 has a distinct localization to endothelial cells and the basal plasma membrane of virtually all epithelial cells in the bronchi and most cells in the terminal bronchioles.
6. Further enrichment of epithelial cfus in the EpCAMhi cell fraction was achieved by selecting on the basis of high or low expression of CD24 (heat-stable antigen) the incidence of colony formation is directly proportional to the number of CD24low cells plated and that the cloning efficiency of this population is only about 4.5%
7. Only CD24low cells demonstrate cfu potential, suggesting that only a restricted subpopulation of EpCAM^hi CD49f^pos CD104^pos CD24^low bronchiolar epithelial cells have the capacity to serve as stem/progenitor cells
1. This is at variance with previous reports suggesting that the majority of Clara cells in the bronchioles can self-renew and generate differentiated progeny (13). The relation of the authors EpCAMhi CD24low population to the Clara or variant Clara cell is unclear (3) and will require identification of previously undescribed Clara cell markers for further subsetting.
8. Lung epithelial cfus are clonally derived and a subset of EpCAM^hi CD104^pos epthelial cfus possess the capacity for in vitro self-renewal after serial passage.
9. Lung epithelial cfus also contain three distinct subtypes of epithelial colonies:
1. Large airway-like cystic spaces with well-defined lumens: express MUC5AC but not proSP-C and genes encoding airway lineage markers (Foxj1, P63, MUC5AC, CFTR), observe cilia in cells in inner lumen--cells of airway origin
2. Small dense saccular colonies: express proSP-C but not MUC5AC and genes encoding alveolar markers (ABCA3, CEBP/alpha, SP-C, SP-A)--alveolar AEC II cells
3. Clara cell marker (CCSP) overexpressed in cystic and mixed colonies but also detected in saccular colonies
4. Colonies of mixed phenotype with distinct budding: express both MUC5AC and proSP-C (but only at tips of buds)
10. Evidence of adult lung epithelial stem/progenitor cell in adult mouse lung is forthcoming and mostly inferential.

Comments

[Jessica Shaw]

Hi

My name is Jessica Shaw. I've just visited your website
and I was wondering if you'd be interested in
exchanging links with my website. I can offer you a Home Page link back
from 2 of my Health Guide websites which are:

http://www.scchiropractic.com/ with page rank 3
http://www.calltrol.net/ with page rank 3

If you are interested, please add the following information to your
website and kindly let me know when it's ready. I'll do the same for
you in less than 24 hours, otherwise you can delete my link from your
site.

Title: Asbestos Help
URL: http://www.asbestosvictimadvice.com
Description:Information and advice about asbestos related illness and
compensation.

I hope you have a nice day and thank you for your time.

Best regards;

Jessica Shaw
jessica.shaw@scchiropractic.com
Web Marketing Consultant