Author ORCID Identifier
0000-0002-0143-9141
Date of Graduation
12-2019
Document Type
Thesis (MS)
Program Affiliation
Biomedical Sciences
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Ellen Richie
Committee Member
David Johnson
Committee Member
Francesca Cole
Committee Member
Mark Bedford
Committee Member
Stephanie Watowich
Abstract
T-cells develop in the thymus based on signaling from multiple stromal cell types, particularly thymic epithelial cells (TECs). The thymus develops rapidly during the perinatal time period (birth – 10 days in mice) before reaching a period of homeostasis (10 days – 6 weeks). The mechanisms that initially promote and subsequently limit expansion of the TEC compartment are not known. However, previous reports from our lab suggest that the Cyclin D1-RB-E2F pathway plays a key role in regulating the perinatal to adult transition. We have previously shown that inactivation in TEC of retinoblastoma (RB) family members through deletion of RB family members or expression of cyclin D1 maintains perinatal-like TEC proliferation and continued thymus expansion.
Although both cortical TEC (cTEC) and medullary TEC (mTEC) are expanded in the K5.D1 thymus, FACs analysis revealed a marked increase in a novel UEA-1int Sca-1- TEC subset, which is not readily classified as belonging to either the cTEC or mTEC lineage. In addition, low level expression of MHC class II and high-level expression of CD24 suggest that the UEA-1int Sca-1- subset contains immature TECs. Cells with this phenotype constitute a small subset of TEC in the wildtype thymus. The K5.D1 UEA-1int Sca-1- subset has a higher proliferative index compared to the wildtype subset.
Keywords
Thymus, Thymic Epithelial Cells, Perinatal