An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.
An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.
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DOI：
10.1038/ncb3023
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发表时间：
2014-09
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
再生医学的一个中心目标是从体外衍生或扩增的细胞中产生可移植器官。尽管许多研究已经证明了在体外产生确定的细胞类型，但尚未报道产生完全完整的器官。转录因子叉头盒N1（FOXN1）是胸腺上皮细胞（TEC）发育所必需的，TEC是胸腺基质的关键细胞类型。在这里，我们表明，强制Foxn1的表达是足够的重新编程成纤维细胞成功能TEC，一个不相关的细胞类型跨越生殖层边界。这些Foxn1诱导的TEC（iTEC）支持CD4+和CD8+ T细胞在体外的有效发育。移植后，iTEC建立了一个完整的，完全组织和功能性的胸腺，其中包含支持T细胞分化所需的所有TEC亚型，并用T细胞填充受体免疫系统。因此，iTEC证明细胞重编程方法可用于产生整个器官，并打开了广泛使用胸腺移植来增强患者免疫功能的可能性。
A central goal of regenerative medicine is to generate transplantable organs from cells derived or expanded in vitro. Although numerous studies have demonstrated production of defined cell-types in vitro, creation of a fully intact organ has not been reported. The transcription factor Forkhead box N1 (FOXN1) is critically required for development of thymic epithelial cells (TECs) a key cell-type of the thymic stroma. Here, we show that enforced Foxn1 expression is sufficient to reprogramme fibroblasts into functional TECs, an unrelated cell-type across a germ-layer boundary. These Foxn1-induced TECs (iTECs) supported efficient development of both CD4+ and CD8+ T cells in vitro. Upon transplantation, iTEC established a complete, fully organized and functional thymus, that contained all of the TEC sub-types required to support T cell differentiation and populated the recipient immune system with T cells. iTEC thus demonstrate that cellular reprogramming approaches can be used to generate an entire organ, and open the possibility of widespread use of thymus transplantation to boost immune function in patients.
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影响因子：
23.9
作者：
Parent, Audrey V.;Russ, Holger A.;Khan, Imran S.;LaFlam, Taylor N.;Metzger, Todd C.;Anderson, Mark S.;Hebrok, Matthias
通讯作者：
Hebrok, Matthias
影响因子：
4.6
作者：
Hameyer, Dorothe;Loonstra, Ate;Bockamp, Ernesto
通讯作者：
Bockamp, Ernesto
影响因子：
158.5
作者：
Markert, ML;Boeck, A;Mahaffey, SM
通讯作者：
Mahaffey, SM
影响因子：
20.3
作者：
Lai, Laijun;Cui, Cheng;Zhao, Yong
通讯作者：
Zhao, Yong
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW