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

## TL;DR

This study identifies and characterizes stem cells in the human thymus that can form epithelial cells, revealing new insights into T-cell development.

## Contribution

The study uncovers previously unknown characteristics of epithelial progenitor cells in the human thymus.

## Key findings

- Neonatal and adult thymuses produce similar numbers of spheroids, indicating consistent progenitor potential.
- Spheroids contain cells expressing genes of both mature and immature epithelial cells.
- Treatment with 2-deoxyguanosine improved progenitor cell yield, and Cyr61 and Interleukin-22 affected spheroid size.

## Abstract

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.