Thyroid Hormone Signaling in Embryonic Stem Cells: Crosstalk with the Retinoic Acid Pathway

• Published in: International journal of molecular sciences Vol. 21; no. 23; p. 8945
• Main Authors: Fernández, Mercedes, Pannella, Micaela, Baldassarro, Vito Antonio, Flagelli, Alessandra, Alastra, Giuseppe, Giardino, Luciana, Calzà, Laura
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-11-2020; MDPI
• Subjects: Animals; Cell adhesion & migration; Cell differentiation; Cell Differentiation - drug effects; Cell Line; Cell Lineage - genetics; Crosstalk; Differentiation; Embryo cells; Embryogenesis; Embryoid Bodies - drug effects; Embryonic Development - genetics; embryonic stem cells; Embryonic Stem Cells - metabolism; Embryos; Enzymes; Female; Fetuses; Gene expression; Hormones; Hypothyroidism; Ligands; Maturation; mRNA; Nestin; Neural Plate - growth & development; Neural Plate - metabolism; Neuroectoderm; Nuclear receptors; Population; Pregnancy; Proteins; Rats; Receptors, Thyroid Hormone - antagonists & inhibitors; Receptors, Thyroid Hormone - genetics; Retinoic acid; Signal Transduction - drug effects; Stem cell transplantation; Stem cells; Thyroid gland; thyroid hormone; Thyroid hormones; Thyroid Hormones - genetics; Thyroid Hormones - metabolism; Transcription factors; Tretinoin - metabolism; Vitamin A; nuclear receptors; retinoic acid; thyroid hormone; embryonic stem cells; neuroectoderm; nestin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21238945

While the role of thyroid hormones (THs) during fetal and postnatal life is well-established, their role at preimplantation and during blastocyst development remains unclear. In this study, we used an embryonic stem cell line isolated from rat (RESC) to study the effects of THs and retinoic acid (RA) on early embryonic development during the pre-implantation stage. The results showed that THs play an important role in the differentiation/maturation processes of cells obtained from embryoid bodies (EB), with thyroid hormone nuclear receptors (TR) (TRα and TRβ), metabolic enzymes (deiodinases 1, 2, 3) and membrane transporters (Monocarboxylate transporters -MCT- 8 and 10) being expressed throughout in vitro differentiation until the Embryoid body (EB) stage. Moreover, thyroid hormone receptor antagonist TR (1-850) impaired RA-induced neuroectodermal lineage specification. This effect was significantly higher when cells were treated with retinoic acid (RA) to induce neuroectodermal lineage, studied through the gene and protein expression of nestin, an undifferentiated progenitor marker from the neuroectoderm lineage, as established by nestin mRNA and protein regulation. These results demonstrate the contribution of the two nuclear receptors, TR and RA, to the process of neuroectoderm maturation of the in vitro model embryonic stem cells obtained from rat.