Date of Graduation
5-2016
Document Type
Thesis (MS)
Program Affiliation
Experimental Therapeutics
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
George T. Eisenhoffer Jr.
Committee Member
Zahid Siddik
Committee Member
Richard Behringer
Committee Member
Jichao Chen
Committee Member
Michael J. Galko
Abstract
Homeostatic maintenance of epithelia requires the renewal and replacement of old or dying cells while sustaining a functional barrier. Imbalance between cell production and elimination are hypothesized to underlie many pathological conditions. However, our knowledge of cell turnover within living tissues remains largely restricted to static images due to the limited ability to study epithelia in their native context. Here we report that clearance of damaged basal stem cells promotes compensatory proliferation of neighboring stem cells to maintain overall population numbers in a bilayered epithelium. Time-lapse imaging and electron microscopy experiments reveal that dying cells are rapidly cleared as nearby basal cells engulf apoptotic debris. Remaining basal cells subsequently divide to replace lost cells, allowing for conservation of tissue integrity and function. Together, our data demonstrate the ability to study and visualize the dynamics of epithelial stem cell turnover during tissue homeostasis with in vivo time-lapse imaging. This approach has the ability to rapidly reveal novel mechanisms regulating epithelial tissue homeostasis and will further our understanding of how these processes become altered in disease.
Keywords
cell turnover, homeostasis, epithelia, epithelial bilayer, stem cell, zebrafish, danio rerio