Transcriptomic Profiles of Normal Pituitary Cells and Pituitary Neuroendocrine Tumor Cells

Abstract

The pituitary gland is one of the most cellularly diverse regions of the brain. Recent advancements in transcriptomic biology, such as single-cell RNA sequencing, bring an unprecedented glimpse into the molecular composition of the pituitary, both in its normal physiological state and in disease. Deciphering the normal pituitary transcriptomic signatures provides a better insight into the ontological origin and development of five types of endocrine cells, a process involving complex cascades of transcription factors that are still being established. In parallel with these observations about normal pituitary development, recent transcriptomic findings on pituitary neuroendocrine tumors (PitNETs) demonstrate both preservations and changes in transcription factor expression patterns compared to those seen during gland development. Furthermore, recent studies also identify differentially expressed genes that drive various tumor behaviors, including hormone hypersecretion and tumor aggression. Understanding the comprehensive multiomic profiles of PitNETs is essential in developing molecular profile-based therapies for PitNETs not curable with current treatment modalities and could eventually help align PitNETs with the breakthroughs being made in applying precision medicine to other tumors.

Keywords: Cushing; gonadotroph; pituitary; pituitary adenomas; pituitary neuroendocrine tumors; prolactinoma; scRNA-seq; transcriptomics.

Figure 1

Specific transcription factors drive normal pituitary cell differentiation during development. Pituitary stem cells differentiate into five specialized, endocrine hormone-producing cell types: corticotrophs (ACTH), somatotrophs (GH), lactotrophs (prolactin), thyrotroph (TSH), and gonadotrophs (LH and FSH). Pituitary cell differentiation requires a complex cascade of transcription factors, many of which are still in the process of being identified. Only select transcription factors are highlighted in this diagram.

Figure 2

Transcriptomic profiling of pituitary neuroendocrine tumors. (TOP) A transcriptome captures a snapshot in time of diverse transcripts present in a pituitary tumor cell. Microarrays capture a set of predetermined sequences whereas single-cell RNA sequencing and bulk RNA sequencing capture all transcripts using high-throughput sequencing. In contrast to bulk RNA sequencing, single-cell RNA sequencing can identify and analyze cell subpopulations. (BOTTOM) Transcriptomic analysis reveals differentially expressed genes that drive various tumor behaviors, such as hormone hypersecretion and tumor invasiveness. Transcriptomic changes in a corticotroph tumor cell are highlighted in this diagram.