Single-cell transcriptome analysis reveals thyrocyte diversity in the zebrafish thyroid gland

Area of Science:

• Endocrinology
• Cell Biology
• Developmental Biology

Background:

• The thyroid gland regulates crucial physiological processes like growth and metabolism through thyroid hormone production.
• Thyrocytes, the cells forming thyroid follicles, have been traditionally considered a uniform population.
• Understanding thyrocyte heterogeneity is key to a comprehensive view of thyroid function.

Purpose of the Study:

• To investigate potential heterogeneity within the thyrocyte population.
• To molecularly characterize non-thyrocyte cells in the zebrafish thyroid gland region.
• To identify distinct subpopulations of thyrocytes and their molecular profiles.

Main Methods:

• Development of a single-cell transcriptome atlas of the zebrafish thyroid gland region, encompassing 6249 cells.
• Analysis of cell types including thyrocytes, vascular, immune, and fibroblast cells.
• Generation of a CRISPR/Cas9-based pax2a knock-in zebrafish line to track pax2a expression in thyrocytes.

Main Results:

• The single-cell atlas revealed heterogeneity in thyrocyte gene expression, notably bimodal expression of the transcription factor pax2a.
• Validation using the pax2a knock-in line identified a distinct population of pax2a-low mature thyrocytes within follicles.
• RNA sequencing of pax2a-high and pax2a-low thyrocytes showed 20% differential gene expression between these subpopulations.

Conclusions:

• Thyrocytes are not a homogenous cell population as previously assumed.
• Transcriptional differences exist between distinct thyrocyte subpopulations, exemplified by pax2a expression levels.
• This study provides a foundational resource for understanding thyroid cell diversity and function.