Directed differentiation of mouse embryonic stem cells into thyroid follicular cells

被引:53
作者
Arufe, Maria C.
Lu, Min
Kubo, Atsushi
Keller, Gordon
Davies, Terry F.
Lin, Reigh-Yi
机构
[1] Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Dept Med, Beijing 100029, Peoples R China
[2] Mt Sinai Sch Med, Dept Gene & Cell Med, Beijing 100029, Peoples R China
[3] Nara Med Univ, Dept Publ Hlth, Nara 6348521, Japan
[4] James J Peters Vet Adm Med Ctr, Div Endocrinol & Metab, Bronx, NY 10468 USA
关键词
D O I
10.1210/en.2005-1239
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Elucidating the molecular mechanisms leading to the induction and specification of thyroid follicular cells is important for our understanding of thyroid development. To characterize the key events in this process, we previously established an experimental embryonic stem (ES) cell model system, which shows that wild-type mouse CCE ES cells can give rise to thyrocyte-like cells in vitro. We extend our analysis in this report by using a genetically manipulated ES cell line in which green fluorescent protein (GFP) cDNA is targeted to the TSH receptor (TSHR) gene, linking GFP expression to the transcription of the endogenous TSHR gene. The appearance of GFP-positive cells was dependent on the formation of embryoid bodies from undifferentiated ES cells and was greatly enhanced by TSH treatment during the first 2-4 d of differentiation. With the support of Matrigel, highly enriched ES cell-derived GFP-positive cells formed thyroid follicle-like clusters in a serum-free medium supplemented with TSH. Importantly, these clusters display the characteristics of thyroid follicular cells. Immunofluorescent studies confirmed the colocalization of TSHRwith the Na+/I- symporter in the clusters and indicated that Na+/I- symporter was expressed exclusively in the plasma membrane. In addition, I- uptake activity was observed in these cells. Our results indicate that ES cells can be induced to differentiate into thyroid follicular cells, providing a powerful tool to study embryonic thyroid development and function.
引用
收藏
页码:3007 / 3015
页数:9
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