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- Title
Single-cell RNA sequencing in silent corticotroph tumors confirms impaired POMC processing and provides new insights into their invasive behavior.
- Authors
Dongyun Zhang; Hugo, Willy; Bergsneider, Marvin; Wang, Marilene B.; Won Kim; Vinters, Harry V.; Heaney, Anthony P.
- Abstract
Objective: Provide insights into the defective POMC processing and invasiv e behavior in silent pituitary corticotroph tumors. Design and methods: Single-cell RNAseq was used to compare the cellular makeup and transcriptome of silent and active corticotroph tumors. Results: A series of transcripts related to hormone processing peptidas es and genes involved in the structural organization of secretory vesicles were reduced in silent compa red to active corticotroph tumors. Most relevant to their invasive behavior, silent corticotroph tumors exhibited s everal features of epithelial-to-mesenchymal transition, with increased expression of mesenchymal genes along with the l oss of transcripts that regulate hormonal biogenesis and secretion. Silent corticotroph tumor vascular smooth muscle cell and pericyte stromal cell populations also exhibited plasticity in their mesenchymal features. Conclusions: Our findings provide novel insights into the mechanisms of impa ired POMC processing and invasion in silent corticotroph tumors and suggest that a common transcript ional reprogramming mechanism simultaneously impairs POMC processing and activates tumor invasion.
- Subjects
RNA sequencing; VASCULAR smooth muscle; SECRETORY granules; SMOOTH muscle tumors; PITUITARY tumors; TUMOR suppressor genes; SOMATIC mutation; COAT proteins (Viruses)
- Publication
European Journal of Endocrinology, 2022, Vol 187, Issue 1, p49
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-21-1183