Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus
Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus
复制标题
DOI：
10.1016/j.celrep.2014.07.029
复制
发表时间：
2014-08-21
期刊：
影响因子：
8.8
通讯作者：
Chidgey, Ann P.
中科院分区：
文献类型：
--
作者：
Wong, Kahlia;Lister, Natalie L.;Chidgey, Ann P.
胸腺上皮细胞 (TEC) 对于 T 细胞发育和自我耐受至关重要，但会随着年龄的增长而逐渐丧失。人们已经推断出生后胸腺中存在胸腺上皮祖细胞（TEPC），但它们的身份仍然是个谜。在这里，我们评估了整个成人 TEC 区室，以揭示祖细胞能力仅保留在未成熟胸腺上皮的子集中，显示出干细胞/祖细胞功能的几个标志性特征。这些成年 TEPC 在胎儿胸腺重新聚集移植物中逐步生成成熟的皮质和髓质谱系，包括 Aire+ TEC。尽管在体内相对静止，但成年 TEPC 在体外表现出显着的集落形成和自我更新。重要的是，3D 培养的 TEPC 在返回体内胸腺微环境时保留了分化为皮质和髓质 TEC 谱系的能力。没有其他产后 TEC 子集表现出这种特性组合。成人 TEPC 的表征将有助于理解衰老和再生中的 TEC 生物学。
Thymic epithelial cells (TECs) are critical for T cell development and self-tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs) in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration.