Table_3_Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation.xlsx

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至4周便已启动分化程序。以甲状腺滤泡内出现胶质为标志的功能分化启动，发生于妊娠第10至11周。至妊娠第12至13周时，功能分化完全完成，甲状腺虽分泌水平较低，但已具备合成甲状腺激素的能力。在成熟阶段，甲状腺激素的分泌量逐步提升，甲状腺激素合成调控的生理机制也逐步建立完善。本研究通过对覆盖妊娠第7至11周的人类甲状腺组织开展转录组学分析（transcriptomic analysis），并与成人甲状腺组织进行对照，追踪了人类发育过程中甲状腺功能分化与成熟的完整进程。通过将胚胎及成人甲状腺组织与对应时期的非甲状腺组织进行比对，我们分别获取了胚胎期与成人期人类甲状腺的特异性转录组特征。我们鉴定出一条不依赖促甲状腺激素（thyroid stimulating hormone, TSH）的甲状腺从分化向成熟转变的路径。本研究同时尝试阐明在该妊娠年龄窗口期（此阶段促甲状腺激素尚未出现）中，能够替代TSH以启动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，本研究是首个针对人类胚胎期甲状腺开展转录组学分析并与成人甲状腺组织进行对照的研究。