Differentiation of murine embryonic stem cells to thyrocytes requires insulin and insulin-like growth factor-1.
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.
Arufe
Maria C
MC
Department of Medicine, Mount Sinai School of Medicine, Box 1055, One Gustave L. Levy Place, New York, NY 10029, USA.
Lu
Min
M
Lin
Reigh-Yi
RY
D028341:Activins / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D024002:HMGB Proteins / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology
C496503:Foxa2 protein, mouse; D024002:HMGB Proteins; D007328:Insulin; D011989:Receptors, Thyrotropin; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; C422405:activin A; C519530:insulin-like growth factor-1, mouse; D028341:Activins; D051542:Hepatocyte Nuclear Factor 3-beta; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin