Oral Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Multi-lineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. (#13)

Kahlia Wong 1 , Natalie Lister 1 , Marco Barsanti 1 , Joanna MC Lim 1 , Maree Hammett 1 , Danika Khong 1 , Chris Siatskas 1 , Daniel Gray 2 , Richard Boyd 1 , Ann Chidgey 1
  1. Anatomy and Developmental Biology, Monash University, Clayton, Melbourne, VIC, Australia
  2. Molecular Genetics of Cancer, Walter and Eliza Hall Institute, Melbourne, VIC, Australia
Thymic epithelial cells are critical for T cell development and self-tolerance. However, the thymus gradually involutes with age, which paradoxically begins early in life, leading to >75% loss of function by mid-life and hence profound decrease in naïve T cell production. A central feature to thymic involution is the loss in epithelial cells, the mechanisms for which remain unresolved.
While the fetal thymus has been widely investigated, progress in the adult has been hindered due to difficulties in isolation techniques of thymic epithelial cells, which make up less than 1% of the total adult thymus cellularity, and lack of adult TEC functional validation assays. The existence of thymic epithelial progenitor or stem cells in the adult has been inferred, however, they have not been phenotypically identified or characterised, nor has the sequence of postnatal cortical and medullary epithelial cell generation been determined.

Through a combination of comprehensive cellular and molecular characterisation, in vivo turnover and functional analysis by 3D in vivo reaggregate organ culture and our newly described in vitro culture system, we have for the first time identified an adult thymic epithelial progenitor population contained within a subset of phenotypically immature cortical epithelium. We have demonstrated their self-renewal, colony forming potential and importantly, the generation of mature cortical and medullary cell lineages, including the autoimmune regulator (Aire)+ medullary subset. We have also demonstrated for the first time that generation of adult thymic epithelial cell lineages shows a similar hierarchy to fetal thymus, with medullary lineages differentiating from cortical precursors. 

The identification of adult thymic epithelial progenitor cells will provide an important catalyst for the field to progress investigations into the molecular regulation of these critical cells during homeostasis, differentiation and regeneration following damage, and degeneration with age. In the longer term, this will enable more strategically targeted approaches for therapeutic thymic regeneration. 

  1. Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. Wong K, Lister NL, Barsanti M, Lim JM, Hammett MV, Khong DM, Siatskas C, Gray DH, Boyd RL, Chidgey AP. Cell Reports 2014 Aug 21;8(4):1198-209.