The Cellular and Molecular Characteristics of Postnatal Human Thymus Stromal Stem Cells.

Background

The thymus is the central hub of T-cell differentiation, where epithelial cells guide the process of their maturation.

Objective

Our goal was to identify and describe progenitor cells within the human thymus that can differentiate into epithelial cells.

Methods

When we plated enriched thymic cells in 3D culture conditions, rare individual cells capable of self-renewal and differentiation formed spheroids.

Results

Both neonatal and adult thymuses produced similar numbers of spheroids, suggesting that progenitor potential remains consistent across age groups. Some cells within the spheres express genes typical of mature epithelial cells, while others express genes associated with the immature compartment active during thymic organogenesis. However, there were also cells expressing PDGFRβ. We treated the tissues with 2-deoxyguanosine before digestion, which improved the yield of progenitor cells. We also cultured the enriched stromal thymocytes with Cyr61 and Interleukin-22, which affected the spheroid size.

Conclusions

Our efforts towards thymic reconstitution are ongoing, but our research uncovers previously unknown characteristics of the elusive epithelial progenitor population.