Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors
Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors
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DOI：
10.1016/j.celrep.2015.10.012
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发表时间：
2015-11-17
期刊：
影响因子：
8.8
通讯作者：
Takahama, Yousuke
中科院分区：
文献类型：
--
作者：
Ohigashi, Izumi;Zuklys, Saulius;Takahama, Yousuke
胸腺髓质上皮细胞（mTECs）在T细胞自我耐受的建立中起重要作用。mtec起源于能产生mtec和皮质TEC （ctec）的双能TEC祖细胞，尽管也有mtec受限祖细胞的报道。在这里，我们报告了在小鼠的特定时期内转录β 5t的细胞的体内命运定位分析，β 5t是一种在双能祖细胞中表达的cTEC性状。我们发现，在成年小鼠中，大多数mtec来源于胚胎发生和新生儿期至1周龄期间转录β 5t的祖细胞。成人β 5t（+）祖细胞的贡献很小，即使在损伤引发的再生过程中也是如此。我们的研究结果进一步表明，成年mtec限制性祖细胞来源于围产期β 5t（+）祖细胞。这些结果表明，成年胸腺髓上皮是由mtec谱系细胞维持和再生的，这些细胞在早期个体发育过程中已经过了双能期。
Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe beta 5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe beta 5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult beta 5t(+) progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal beta 5t(+) progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny.