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Multi-omic profiling of pituitary thyrotropic cells and progenitors
Alexandre Z Daly1, Lindsey A Dudley1, Michael T Peel2,3
1Department Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
BMC Biology
|April 16, 2021
Summary
Researchers identified key regulatory elements and transcription factors driving pituitary thyrotrope cell development. This work advances understanding of pituitary development and disease by mapping transcriptional landscapes.
Area of Science:
- Neuroendocrinology
- Molecular Biology
- Genomics
Background:
- The pituitary gland is crucial for regulating physiology via hormone secretion.
- Thyrotropes produce thyroid-stimulating hormone (TSH), vital for metabolism.
- Transcription factors POU1F1 and GATA2 are linked to thyrotrope fate, but their regulatory landscapes are unknown.
Purpose of the Study:
- To discover transcriptional regulatory elements controlling thyrotrope cell differentiation.
- To characterize the transcriptomic and epigenomic landscapes of pituitary thyrotropes.
Main Methods:
- Comparative analysis of RNA-seq, ATAC-seq, and histone modifications (H3K27Ac, H3K4Me1, H3K27Me3) in progenitor and thyrotrope cell lines.
- Mapping POU1F1 binding sites and associated transcription factor motifs.
- Functional validation of novel enhancer elements using transfection and transgenic mouse models.
Main Results:
- Identified distinct transcription factor binding profiles associated with POU1F1 in progenitor versus thyrotrope cells.
- Validated enhancer activity of novel elements near key genes (Cga, Pitx1, Gata2, Tshb).
- Demonstrated GATA2 enhances Tshb expression via a specific enhancer in thyrotropes.
Conclusions:
- This study extends multi-omic profiling to the pituitary gland.
- Findings provide insights into the transcriptional regulation of thyrotrope development.
- The data will aid in understanding pituitary development and associated diseases.
