SAT-081 - Landscapes in Human Pituitary Cell Type Specific Transcriptome Profiles and Comparison with Functioning Pituitary Tumors by Digital Spatial Profiler.

Pituitary tumors are typically benign but can cause profound endocrine dysregulation due to altered hormone secretion levels. A major barrier to understanding pituitary tumorigenesis is the scarcity of high resolution, lineage specific transcriptional data from normal human pituitary tissue. Here, we applied spatial transcriptomics using the NanoString GeoMx Digital Spatial Profiler to generate a comprehensive atlas of the human anterior pituitary. We profiled over 18,000 transcripts across five normal hormone secreting lineages (POMC, GH, PRL, TSH, FSH) and compared them to corticotroph adenomas (Cushing’s disease; CD) and somatotroph adenomas (acromegaly; Acro).
In normal pituitary cells, comparing the 5 major lineages to each other revealed the POMC cells to have the highest transcriptional activity (with over 60% of over expressed genes belonging to POMC). Most of these genes are related to stress, growth, and metabolic signaling. Conversely, GH and TSH lineages appeared relatively quiescent. We further used machine leaning methods and detected 2 unique genes to differentiate pituitary lineages.
We also compared tumors and normal cells (POMC cells vs. CD, and GH cells vs Acro). CD displayed relative transcriptional quiescence compared to normal POMC cells in our profile; In Acro, there was a significant alteration in genes relating to immune signaling, along with a general upregulation of genes related to neuroendocrine secretion to regulate metabolism. For the subclass analysis of Acro, gene profiles differentiated between densely and sparsely granulated tumors; upregulated hormonal and stromal markers in dense tumors, whereas elevated immune and chemokine signaling were seen in sparse tumors. Upregulation of circadian rhythm signaling pathways (PER1/2 and CRY2) was specific to CD. We also detected that PRL was consistently upregulated across both CD and Acro and speculated PRL upregulation may contain a potential multi-hormonal feature in these tumors.
Our spatially resolved atlas provides a high-resolution, cell-type-specific map of human pituitary diversity. Our study will help establish a molecular baseline for understanding pituitary pathologies and identifying novel biomarkers for targeted therapeutic intervention.

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