Table_5_Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation.docx

The human thyroid gland acquires a differentiation program as early as weeks 3–4 of embryonic development. The onset of functional differentiation, which manifests by the appearance of colloid in thyroid follicles, takes place during gestation weeks 10–11. By 12–13 weeks functional differentiation is accomplished and the thyroid is capable of producing thyroid hormones although at a low level. During maturation, thyroid hormones yield increases and physiological mechanisms of thyroid hormone synthesis regulation are established. In the present work we traced the process of thyroid functional differentiation and maturation in the course of human development by performing transcriptomic analysis of human thyroids covering the period of gestation weeks 7–11 and comparing it to adult human thyroid. We obtained specific transcriptomic signatures of embryonic and adult human thyroids by comparing them to non-thyroid tissues from human embryos and adults. We defined a non-TSH (thyroid stimulating hormone) dependent transition from differentiation to maturation of thyroid. The study also sought to shed light on possible factors that could replace TSH, which is absent in this window of gestational age, to trigger transition to the emergence of thyroid function. We propose a list of possible genes that may also be involved in abnormalities in thyroid differentiation and/or maturation, hence leading to congenital hypothyroidism. To our knowledge, this study represent the first transcriptomic analysis of human embryonic thyroid and its comparison to adult thyroid.

人类甲状腺在胚胎发育的第3~4周即启动分化程序。其功能分化的起始以甲状腺滤泡内出现胶体为标志，发生于妊娠第10~11周。至妊娠第12~13周时，功能分化全面完成，甲状腺虽分泌水平较低，但已能够合成并分泌甲状腺激素。在甲状腺成熟阶段，甲状腺激素的分泌量逐步升高，甲状腺激素合成调控的生理机制也逐渐建立完善。

本研究通过对妊娠第7~11周的人类甲状腺组织开展转录组学分析，并将其与成人甲状腺组织进行对比，追踪了人类发育过程中甲状腺功能分化与成熟的动态进程。通过将人类胚胎甲状腺与成人甲状腺组织，分别与对应胚胎及成人的非甲状腺组织进行比对，我们鉴定得到了人类胚胎及成人甲状腺特有的转录组特征。我们明确了一条不依赖于促甲状腺激素（thyroid stimulating hormone, TSH）的甲状腺分化至成熟的转化路径。本研究同时尝试阐明，在该妊娠窗口期内缺乏TSH的情况下，可替代TSH以触发甲状腺功能出现的潜在调控因子。我们提出了一系列可能参与甲状腺分化和/或成熟异常、进而导致先天性甲状腺功能减退症的候选基因。据我们所知，本研究是首次针对人类胚胎甲状腺开展转录组学分析并与成人甲状腺进行对比的研究。