Dom Geneviève, Dmitriev Petr, Lambot Marie-Alexandra, Van Vliet Guy, Glinoer Daniel, Libert Frédérick, Lefort Anne, Dumont Jacques E, Maenhaut Carine
School of Medicine, IRIBHM, Université libre de Bruxelles, Brussels, Belgium.
Institute of Interdisciplinary Research in Human and Molecular Biology, Brussels, Belgium.
Front Cell Dev Biol. 2021 Jun 11;9:669354. doi: 10.3389/fcell.2021.669354. eCollection 2021.
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.
人类甲状腺早在胚胎发育的第3 - 4周就开始获得分化程序。功能性分化的开始表现为甲状腺滤泡中出现胶体,发生在妊娠第10 - 11周。到12 - 13周时,功能性分化完成,甲状腺能够产生甲状腺激素,尽管水平较低。在成熟过程中,甲状腺激素产量增加,甲状腺激素合成调节的生理机制得以建立。在本研究中,我们通过对妊娠第7 - 11周的人类甲状腺进行转录组分析,并将其与成人甲状腺进行比较,追踪了人类发育过程中甲状腺功能分化和成熟的过程。我们通过将胚胎和成人甲状腺与人类胚胎和成人的非甲状腺组织进行比较,获得了它们特定的转录组特征。我们定义了一种不依赖促甲状腺激素(TSH)的甲状腺从分化到成熟的转变。该研究还试图阐明在这个胎龄期不存在的促甲状腺激素可能被哪些因素替代,从而触发向甲状腺功能出现的转变。我们提出了一份可能也参与甲状腺分化和/或成熟异常、进而导致先天性甲状腺功能减退的基因清单。据我们所知,这项研究是对人类胚胎甲状腺及其与成人甲状腺比较的首次转录组分析。