Endocrine Abstracts

Normal functioning of the thyroid is of profound importance for lifetime health due to its role in hormone production. Dysfunction of the thyroid is associated with severe congenital pathologies, some of them appearing in childhood. For example, over half the babies born with congenital hypothyroidism appear completely normal and without symptoms. However, early diagnosis of thyroid defects is lacking mainly due to a poor understanding of the development of the tissue in utero. Here we have established a comprehensive spatiotemporal atlas of the developing human thyroid during the first and second trimester of pregnancy. Our dense profiling of more than 250k cells using single-cell sequencing has revealed the main cell types, their developmental relationships and transcription factors leading to the formation of the thyroid gland. We characterised the early development thyroid specific cell types including thyrocytes, parathyroid gland and parafollicular cells, known as C cells. Notably, we found that thyrocytes are heterogeneous epithelial populations and split thyroid-hormones production between different subsets. We further validated the spatial heterogeneity of thyrocyte subpopulations using multiple spatial transcriptomics methods. Lastly, we derived ligand-receptor interactions that drive the maturation of thyrocytes during development. Our results confirm the division of labour of the thyrocytes, and highlight active cell-cell communications during thyroid gland development. Altogether our analysis exemplifies the division of labour principle observed in other adult tissues also applies to the development of the thyroids, expanding our knowledge of thyroid-hormones synthesis and regulation. Future work includes how the function principles and potential interactions are altered in pathological conditions.