NHLBI Workshop

Resident Cellular Components of the Human Lung:
Current Knowledge and Goals for Research on Cell Phenotyping and Function

Executive Summary

Purpose

The intent of this workshop, held on July 9-10, 2007, was to identify still obscure or novel cellular components of the lung, to determine cell function in lung development and health that impacts on disease, and to decide promising avenues for future research to extract and phenotype these cells.

The Workshop’s agenda was to discuss first the lung’s embryologic development, including progrenitor and stem cells; and then assess cells from three sites and structural tissues within lung: 1) airway cells in bronchial mucosa (epithelial cells, mucus cells and glands, ciliated cells, and neuro-endocrine cells); 2) alveolar unit cells (Type 1, Type 2 and Type 3 (Brush) cells and fibroblasts in the interstitium); and 3) pulmonary vascular cells comparing endothelial cells from different vascular structures, smooth muscle cells and adventitial fibroblasts.

Major Recommendations

Since robust technologies are now available to identify, sort, purify, culture and phenotype cells (by mRNA protein and genomics) progress in unraveling the origins and capabilities of lung cells in development and disease is now within sight.

1. Develop well-characterized cell markers, both surface and non-surface, for the various cells within the lung, including progenitor cells, and stem cells.
2. Precise mRNA array data for various lung cells types can be obtained by various methodologies: dissection, microdissection, and cell isolation sorting. But more knowledge must be obtained about gene expression in specific cell types within the lung in health and disease which will provide insights into biological and pathological processes and will serve as a basis for the development of new cell-specific markers.
3. Develop and apply high throughput assessment of the effects of epigenetics (DNA methylation, histone acetylation and methylation, micro RNAs) on phenotypic characteristics of mesodermal cells under normal and pathological conditions, including misrepair.
4. Develop more new methodologies for cell culture, isolation, sorting, co-culture, and immortalization for various cells. This would be highly useful to the field.
5. Promote more discussion of the definition, identification, and role in the normal and pathological lung of mesenchymal lung “stem cells” to stimulate future research.
   1. For example, what are the triggers and genes involved in ‘transitional states’ in the alveolar compartment? What drives Type 1 to Type 2 differentiation and vice versa, and fibroblast to myofibroblast and vice versa? Is there an epithelial mesenchymal transition (EMT) involved in this compartment?
6. Lung mapping project to harness global strategy to map gene expression/cells in murine and human lung.
7. Develop tissue banks to facilitate the procurement of lung tissue from normal and from diseased lung which would be useful for analysis at all levels, including mRNA, histology, proteomics, and genomics. This would represent a very useful library and promote research.

Working Group Members

Co-Chairs

• Thomas V. Colby, M.D., Mayo Clinic, Scottsdale, AZ
• Teri J. Franks, M.D., Armed Forces Institute of Pathology, Washington, DC
• Rubin M. Tuder, M.D., Johns Hopkins University, Baltimore, MD
• William D. Travis, M.D., Memorial Sloan Kettering Cancer Center, New York, NY

Members

• Arnold R. Brody, Ph.D., North Carolina State University, Raleigh, NC
• Wellington V. Cardoso, M.D., Ph.D., Boston University, Boston, MA
• Ronald G. Crystal, M.D., Weill Medical College of Cornell University, New York, NY
• Christopher J. Drake, Ph.D., Medical University of South Carolina, Charleston, SC
• John Engelhardt, Ph.D., University of Iowa, Iowa City, IA
• Maria Frid, Ph.D., University of Colorado Health Sciences Center, Denver, CO
• Erica Herzog, M.D., Ph.D., Yale University School of Medicine, New Haven, CT
• Robert Mason, National Jewish Medical and Research Center, Denver, CO
• Sem H. Phan, Ph.D., M.D., University of Michigan, Ann Arbor, MI
• Scott H. Randell, Ph.D., University of North Carolina at Chapel Hill, NC
• Troy Stevens, Ph.D., University of South Alabama, Mobile, AL
• Julie Segre, Ph.D., National Human Genome Research Institute, NIH, Bethesda, MD
• Mary E. Sunday, M.D., Ph.D., Duke University, Durham, NC
• Judith A. Voynow, M.D., Duke University, Durham, NC
• Brant M. Weinstein, Ph.D., National Institute of Child Health and Human Development, NIH, Bethesda, MD
• Jeffrey Whitsett, M.D., Children's Hospital Research, Cincinnati, OH
• Mary C. Williams, Ph.D., Boston University, Boston, MA

NHLBI Staff

• Dorothy B. Gail, Ph.D., Division of Lung Diseases, Bethesda, MD
• James P. Kiley, Ph.D., Division of Lung Diseases, Bethesda, MD
• Herbert Y. Reynolds, M.D., Division of Lung Diseases, Bethesda, MD

Last Updated August 2007