Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages.
Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages.
复制标题
DOI：
10.1016/j.immuni.2014.07.005
复制
发表时间：
2014-08-21
期刊：
影响因子：
32.4
通讯作者：
Kyewski, Bruno
中科院分区：
文献类型：
--
作者：
Ucar, Ahmet;Ucar, Olga;Klug, Paula;Matt, Sonja;Brunk, Fabian;Hofmann, Thomas G.;Kyewski, Bruno
在胸腺内，两个主要的胸腺上皮细胞（TEC）亚群——皮质和髓质TEC——为T细胞的发育和中枢耐受性的建立提供了独特的结构和功能龛。这两个谱系被认为起源于一个共同的祖细胞，但这些双能TEC祖细胞/干细胞的细胞和分子身份仍然不明确。在这里，我们在小鼠成年胸腺中发现了罕见的基质细胞，它们在低附着条件下形成球体（称为“胸腺球”）。这些胸腺球形成细胞（tsfc）表现出缓慢循环、自我更新和双能性的干性特征。tsfc由于其不同的表面抗原表型而显著富集。FoxN1转录因子对于tsfc的原位维持和髓质和皮质TEC谱系的承诺是必不可少的。总之，本研究提出了成体胸腺上皮干细胞的特征，并证明了FoxN1功能对其干细胞性的必要性。成人胸腺上皮含有胸腺球形成干细胞（TSFCs）。在体外和体内，TSFCs都能产生胸腺上皮细胞系，在没有FoxN1谱系的情况下，TSFCs在球体中是独立于FoxN1的。出生后胸腺中存在双能性胸腺上皮干细胞一直存在争议。Kyewski和他的同事使用一种球体形成试验来鉴定和表征慢循环、自我更新和双能胸腺上皮干细胞，这些干细胞是独立于转录因子FoxN1产生的。
Within the thymus, two major thymic epithelial cell (TEC) subsets—cortical and medullary TECs—provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed “thymospheres”). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness. Adult thymic epithelium contains thymosphere-forming stem cells (TSFCs) TSFCs give rise to both thymic epithelial lineages in vitro and in vivo TSFCs are maintained in the absence of functional FoxN1 Lineage commitment in the sphere is FoxN1 independent The existence of a bipotent thymic epithelial stem cell in the postnatal thymus has been controversial. Kyewski and colleagues use a sphere-forming assay to identify and characterize slow-cycling, self-renewing, and bipotent thymic epithelial stem cells that are generated independent of transcription factor FoxN1.
登录
查看更多内容
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
人角蛋白：生物学和病理学。
影响因子：
2.3
作者：
Moll, Roland;Divo, Markus;Langbein, Lutz
通讯作者：
Langbein, Lutz
DOI：
10.1084/jem.20070795
发表时间：
2007-10-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gray D;Abramson J;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
56.9
作者：
Murata, Shigeo;Sasaki, Katsuhiro;Tanaka, Keiji
通讯作者：
Tanaka, Keiji
影响因子：
64.8
作者：
NEHLS, M;PFEIFER, D;BOEHM, T
通讯作者：
BOEHM, T