Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus.
Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus.
复制标题
DOI：
10.1016/j.celrep.2016.02.080
复制
发表时间：
2016-03-29
期刊：
影响因子：
8.8
通讯作者：
Blackburn CC
中科院分区：
文献类型：
--
作者：
Ulyanchenko S;O'Neill KE;Medley T;Farley AM;Vaidya HJ;Cook AM;Blair NF;Blackburn CC
胸腺上皮细胞（TEC）是T细胞发育所必需的，但维持成体TEC的细胞机制知之甚少。在这里，我们发现了一个以前未识别的亚群，EpCam+ UEA 1 −Ly-51+ PLET 1 +MHC class IIhi，它包含<0.5%的成年TEC，含有双能TEC祖细胞，可以有效地产生皮质（c）TEC和髓质（m）TEC。本研究中检测的其他成年TEC群体均不含该活性。我们证明持久性PLET 1 +Ly-51+ TEC衍生的细胞在体内9个月，表明胸腺上皮干细胞的存在。此外，我们鉴定了cTEC限制的短期祖细胞活性，但未能在成年胸腺中检测到高效mTEC限制的祖细胞。我们的数据提供了一种表型确定的成人胸腺上皮祖细胞/干细胞，能够产生cTEC和mTEC，为改善患者的胸腺功能开辟了途径。成体PLET 1 + TEC包括PLET 1 + UEA 1 +Ly-51− mTEC和PLET 1 +Ly-51+ UEA 1 − CMJ TEC MHCIIhiPLET 1 +Ly-51+ TEC包括可产生mTEC的双能祖细胞和cTEC Ly-51 + TEC还包含cTEC限制性短期祖细胞PLET 1 +Ly-51+ TEC的后代在体内持续9个月，提示TEC干细胞胸腺上皮细胞（TEC）是T细胞发育所必需的。Ulyanchenko等人使用克隆水平分析来鉴定表型定义的胸腺上皮祖细胞类型。该群体包括<0.5%的成年TEC，并且能够在体内产生皮质和髓质TEC ≥9个月。
Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam+UEA1−Ly-51+PLET1+MHC class IIhi, which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c) TECs and medullary (m) TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1+Ly-51+ TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients. Adult PLET1+ TECs encompass PLET1+UEA1+Ly-51− mTECs and PLET1+Ly-51+UEA1− CMJ TECs MHCIIhiPLET1+Ly-51+ TECs include bipotent progenitors that can generate mTECs and cTECs Ly-51+ TECs also contain cTEC-restricted short-term progenitors Progeny of PLET1+Ly-51+ TECs persist for 9 months in vivo, hinting at TEC stem cells Thymic epithelial cells (TECs) are critically required for T cell development. Ulyanchenko et al. use clonal-level analysis to identify a phenotypically defined thymic epithelial progenitor cell type. This population comprises <0.5% of adult TECs and is able to generate both cortical and medullary TECs for ≥9 months in vivo.