Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1.
Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1.
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DOI：
10.1016/j.bbrc.2009.02.035
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发表时间：
2009-04-03
影响因子：
3.1
通讯作者：
Lin, Reigh-Yi
中科院分区：
文献类型：
--
作者：
Arufe, Maria C.;Lu, Min;Lin, Reigh-Yi
尽管之前的研究表明促甲状腺激素（TSH）参与了胚胎干（ES）细胞分化过程中的甲状腺细胞发育，但控制甲状腺细胞发育的机制仅得到部分阐明。为了进一步明确 TSH 在这方面的作用，我们研究了一种小鼠 ES 细胞系，其中绿色荧光蛋白 (GFP) cDNA 靶向 TSH 受体 (TSHR) 基因，将 GFP 的表达与内源 TSHR 基因的转录联系起来。我们证明，在胚状体形成的初始阶段，激活素 A 和 TSH 诱导表达 Sox17、Foxa2 和 TSHR 的定形内胚层和甲状腺细胞祖细胞的分化。然后，这些甲状腺细胞祖细胞转化为细胞聚集体，在胰岛素和 IGF-1 存在的情况下，进一步分化为表达成熟甲状腺球蛋白的甲状腺细胞。我们的数据表明，尽管 TSH 对于 ES 细胞的甲状腺细胞的诱导和分化很重要，但胰岛素和 IGF-1 对于甲状腺细胞的成熟至关重要。我们的方法为研究早期甲状腺细胞谱系发育的机制提供了强大的体外分化模型。
The mechanisms controlling thyrocyte development during embryonic stem (ES) cell differentiation have only been partially elucidated, although previous studies have suggested the participation of thyroid stimulating hormone (TSH) in these processes. To further define the role of TSH in this context, we have studied a murine ES cell line in which green fluorescent protein (GFP) cDNA is targeted to the TSH receptor (TSHR) gene, linking the expression of GFP to the transcription of the endogenous TSHR gene. We demonstrate that, in the initial stages of embryoid body formation, activin A and TSH induce the differentiation of definitive endoderm and thyrocyte progenitors expressing Sox17, Foxa2 and TSHR. These thyrocyte progenitors are then converted into cellular aggregates that, in the presence of insulin and IGF-1, further differentiate into mature thyroglobulin-expressing thyrocytes. Our data suggest that, despite the fact that TSH is important for the induction and specification of thyrocytes from ES cells, insulin and IGF-1 are crucial for thyrocyte maturation. Our method provides a powerful in vitro differentiation model for studying the mechanisms of early thyrocyte lineage development.
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影响因子：
4.8
作者：
SMERDELY, P;PITSIAVAS, V;BOYAGES, SC
通讯作者：
BOYAGES, SC
影响因子：
4.1
作者：
VENEZIANI, BM;DIMARINO, C;TRAMONTANO, D
通讯作者：
TRAMONTANO, D
影响因子：
4.8
作者：
Arufe, Maria C.;Lu, Min;Lin, Reigh-Yi
通讯作者：
Lin, Reigh-Yi
影响因子：
44.1
作者：
Jiang, Wei;Shi, Yan;Deng, Hongkui
通讯作者：
Deng, Hongkui
影响因子：
3.9
作者：
Chieffi, P;Picascia, A;Tramontano, D
通讯作者：
Tramontano, D