ESPE Yearbook of Paediatric Endocrinology

Brief Summary:This study used single-cell RNA-seq and murine transgenic models combined with elegant cell lineage tracing to characterise the gene expression profiles and trajectories of pituitary thyrotropes. It identifies a novel population of pituitary thyrotropes that co-express Nr5a1 (Sf1) and Pouf1 (Pit1) and a novel developmental trajectory for a subpopulation of Nr5a1-derived thyrotropes.

Classical studies on pituitary cell lineages and cell differentiation considered that gonadotrophs and thyrotropes are derived from different transcription factors, namely Nr5a1 (Sf1, giving rise to gonadotrophs) and Pouf1 (Pit1, thyrotropes, somatotrophs and lactotrophs). However, the transcriptional cascade that leads to thyrotropes-cell lineage specificity is not fully understood. These authors elegantly use single-cell enrichment of thyrotropes cells by using Tshb-Cre;Rosa26-Eyfp followed by cell sorting and single-cell RNA sequencing (scRNA-seq) to identify and characterize the gene expression profiles specific to thyrotropes. Notably, they discover new candidate genes, like Shox2 and Sox14, that play potential roles in the regulation of these cells. Shox2, for instance, was found to show significant expression in thyrotropes and appears to be linked to the transcriptional activity of the TSHβ subunit, a critical component of the thyroid-stimulating hormone. Moreover, in vivo cell lineage tracing using a Foxl2CreERT2 demonstrates the exitance of Pit1-independent dorsal lip thyrotropes.

In conclusion, this study offers significant insights into the development of pituitary thyrotropes, which are crucial to regulate thyroid function. It provides a very useful resource of thyrotropes sc-mRNA-seq data set available to the scientific community. Overall, the study highlights the complexity of pituitary thyrotrope development and opens new avenues for research into the molecular mechanisms underlying thyroid function and its associated disorders.