Skelin Ilic Josipa, Bódi Ildikó, Milkovic Lidija, Prodan Zsolt, Belina Dražen, Heckel Darko, Cicin-Sain Lipa, Grčević Danka, Delfino Domenico Vittorio, Radic Kristo Delfa, Matulić Maja, Antica Mariastefania
Division of Molecular Mediicne, Rudjer Boskovic Institute, 10000 Zagreb, Croatia.
Department of Anatomy, Histology and Embryology, Semmelweis University, 1085 Budapest, Hungary.
Biomedicines. 2025 Apr 21;13(4):1004. doi: 10.3390/biomedicines13041004.
: The thymus is the central hub of T-cell differentiation, where epithelial cells guide the process of their maturation. : Our goal was to identify and describe progenitor cells within the human thymus that can differentiate into epithelial cells. : When we plated enriched thymic cells in 3D culture conditions, rare individual cells capable of self-renewal and differentiation formed spheroids. : 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. : Our efforts towards thymic reconstitution are ongoing, but our research uncovers previously unknown characteristics of the elusive epithelial progenitor population.
胸腺是T细胞分化的中心枢纽,上皮细胞在此引导T细胞的成熟过程。我们的目标是识别并描述人类胸腺内可分化为上皮细胞的祖细胞。当我们将富集的胸腺细胞接种于三维培养条件下时,能够自我更新和分化的罕见单个细胞形成了球体。新生儿和成人胸腺产生的球体数量相似,这表明祖细胞潜能在各年龄组中保持一致。球体内的一些细胞表达成熟上皮细胞的典型基因,而其他细胞则表达与胸腺器官发生过程中活跃的未成熟区室相关的基因。然而,也有细胞表达血小板衍生生长因子受体β(PDGFRβ)。我们在消化前用2-脱氧鸟苷处理组织,这提高了祖细胞的产量。我们还用Cyr61和白细胞介素-22培养富集的基质胸腺细胞,这影响了球体大小。我们在胸腺重建方面的努力仍在继续,但我们的研究揭示了难以捉摸的上皮祖细胞群体以前未知的特征。