SAT-016 Musashi Contributes to the Specification and Maintenance of Distinct Pituitary Cell Lineages.

Abstract Disclosure: J. Banik: None. J. Lim: None. C. Bolen: None. M. Reddick: None. S. Byrum: None. L. Hardy: None. Y. Rahmatallah: None. A.K. Odle: None. G.V. Childs: None. A.M. MacNicol: None. M.C. MacNicol: None. The anterior pituitary regulates multiple organismal functions including growth and development, reproduction and lactation, and metabolism and stress response. Distinct cell populations within the pituitary are required to synthesize and secrete the different hormones that direct these disparate regulatory processes. An insufficiency, or excess, of cells in any population contributes to multiple pathophysiological conditions. The mechanisms by which the distinct cell populations lineages are maintained is not fully understood. Here, we tested a requirement for the stem cell and progenitor cell marker, Musashi, in maintenance of pituitary cell populations. This study utilized a mouse genetic model in which the Musashi1 gene (Msi1) and the Musashi2 gene (Msi2) are deleted in all pituitary hormone producing cell type through use of a Prop1 promoter-driven Cre-lox system. Initial proteogenomic analysis of pituitary from adult male Msi1Msi2-null mice versus control littermates, utilized both mass spectrometry and RNA sequencing from the same sample. Differential expression analyses show a broader impact on the transcriptome than on the proteome profile in Musashi-null mutants. Correlation analysis of differential mRNA expression and differential protein abundance indicates that Musashi represses translation of transcripts that are involved in mRNA processing and localization, and ribonucleoprotein complex assembly and biogenesis, and hormone secretion and transport, all of which would be required for maintenance of hormone-producing pituitary cell populations. Notably, the transcriptomic findings indicate significant increases in a subset of pituitary cell populations e.g. somatotropes (Gh), lactotropes (Prl) and thyrotropes (Tshb), along with a significant decrease in other pituitary cell populations e.g. gonadotropes (Gnrhr), progenitor cells (Pou1f1), and stem cells (Sox2). These findings support a model in which Musashi mediates maintenance of a stem/progenitor pool to ensure an appropriate balance of pituitary cell populations. Presentation: Saturday, July 12, 2025