Studies on the progressive maturation of thymic epithelial progenitors

Baik, Song (2014). Studies on the progressive maturation of thymic epithelial progenitors. University of Birmingham. Ph.D.

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Abstract

The thymus is essential for T-cell development and is histologically divided into two specialized microenvironments: cortex and medulla. The cortex selects functional T cells and the medulla removes potentially auto-reactive T cells. Both selection events are mainly driven by thymic epithelial cells (TECs). However, ageing causes a loss of TECs, consequently resulting in a reduction of thymic function. Several studies have sought to reconstitute thymus function by regenerating TECs, with limited success. We aim to generate thymic tissues from defined sources that may ultimately be transplanted to improve immune function. Moreover, this study seeks to identify TEC progenitors and define distinct TEC developmental pathways, which will ultimately be helpful in understanding both thymic atrophy and thymic regeneration. We show that induced pluripotent stem (iPS) cells can generate functional TECs in vivo. Moreover, our data suggest a serial link between cTEC and mTEC lineage development. Specifically, we find that Aire+ mTEC can develop from progenitors expressing the cTEC marker CD205, and CD205+ progenitors acquire the expression of mTEC regulator Receptor Activator of NF-κB (RANK) before losing their cTEC phenotype. Collectively, our data help clarify potential cellular targets for the re-establishment of functional thymus tissue.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):