Gene Misexpression in a +ve/-Low Population in Juvenile -Mutant Pituitary Gland.

Mutations in the pituitary-specific transcription factor Prophet of Pit-1 () are the most common genetic etiology of combined pituitary hormone deficiency (CPHD). CPHD is associated with short stature, attributable to growth hormone deficiency and/or thyroid-stimulating hormone deficiency, as well as hypothyroidism and infertility. Pathogenic lesions impair pituitary development and differentiation of endocrine cells. We performed single-cell RNA sequencing of pituitary cells from a wild-type and a -mutant P4 female mouse to elucidate population-specific differential gene expression. We observed a +ve population that expressed low , which trajectory analyses suggest are a transitional cell state as stem cells differentiate into endocrine cells. We also detected ectopic expression of in these cells in the mutant. -mutant mice are known to overexpress , which we now show to be also enriched in this +ve population. We sought to elucidate the role of during pituitary development and to determine the contributions of upregulation to pituitary disease by utilizing double-mutant mice lacking both and However, our data showed that is not required for normal pituitary development and function. Double mutants further demonstrated that the upregulation of was not causative for the overexpression of . These data indicate loss of is not a potential cause of CPHD, and further studies may investigate the functional consequence of upregulation of and , if any, in the novel +ve cell population.