DOI

10.17077/etd.cvxsvueb

Document Type

Dissertation

Date of Degree

Summer 2016

Degree Name

PhD (Doctor of Philosophy)

Degree In

Anatomy and Cell Biology

First Advisor

Engelhardt, John F.

First Committee Member

Amendt, Brad A.

Second Committee Member

Slusarski, Diane C.

Third Committee Member

Tootle, Tina L.

Fourth Committee Member

Tucker, Budd A.

Abstract

Breathing is essential for human life, yet tens of millions of people in the U.S. alone suffer from lung diseases. With each breath, lungs are exposed to the external environment. Inhaled air first passes through the trachea, bronchi, and finally the bronchioles before it reaches the alveoli where gases are exchanged. A barrier of epithelial cells protects the airways. In addition, epithelial glands also secrete protein-rich fluids onto the airway surfaces to help maintain sterility. Injury, disease, or other factors can damage these cells, and regiospecific stem cells (SCs) can divide to replace them. However, many important details about lung SCs are still unknown. For example, what processes control SC division? How do region-specific SCs differ from one another? And how does disease or injury impact SC biology? We found that some processes that regulate lung development also control adult SC division following injury. We show that SCs from airway glands give rise to surface epithelial cell types and glandular cell types. In contrast, surface SCs only generated surface cell types. Finally, we identify a type of cell in the glands that can regenerate surface cell types after severe injury. These studies provide new insights into the neighborhoods in which SCs reside in the large airways and processes that control their contribution to airway repair following injury. Overall, this research provides important new insights into adult SC biology and conditions affecting lung health.

Keywords

Adult stem cells, Developmental biology, Facultative stem cell, Multipotential differentiation, Stem cell microenvironment interactions, Stem cell niche

Pages

xi, 159 pages

Bibliography

Includes bibliographical references (pages 148-159).

Comments

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Copyright

Copyright © 2016 Thomas John Lynch

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