ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 3.4 | DOI: 10.1530/ey.18.3.4

EMBO Rep. 2020;21:e50612. doi: 10.15252/embr.202050612.

This zebrafish study identified and molecularly characterized adult transcriptionally different thyrocyte subpopulations even within the same follicle.

It is well established that within a thyroid gland, follicles are heterogenous concerning functional activity. More active follicles are characterized by a high columnar epithelium in contrast to a flat epithelium in inactive follicles [1,2]. Here, Gillotay et al. aimed to characterize the thyrocyte gene expression pattern between follicles and thyrocytes within the same follicle by single cell transcriptome analysis in zebrafish. For this, they established a pax2a gene knock-in reporter line. Further, pax2a expression is the first step of thyroid development in the zebrafish, determining thyrocyte precursors in the zebrafish endoderm [3].

The key findings, first, confirmed thyrocyte heterogeneity in the adult zebrafish thyroid in accordance with earlier reports in human and murine thyroid. Second, they could detect transcriptionally different thyrocytes with low vs. high expression of pax2a not only in different follicles but within the same follicle. Thyrocytes with high pax2a expression showed functional differentiation with expression of the thyroid hormone synthetic machinery (tpo, tg, slc5a5). In contrast, these differentiation markers were not expressed (or only at low levels) in thyrocytes with low pax2a expression. Based on these results, the authors suggest a functional and a resting thyrocyte population within the same follicle. Interestingly, the pax2a low thyrocyte population also showed lower nkx2.4b expression, thus resembling rather a determined thyrocyte progenitor with hypothetically higher proliferative capacity than the pax2a high thyrocyte population.

This knowledge from the zebrafish model provides possible molecular insights, how patient derived adult thyrocyte subpopulations might contribute to tissue regeneration as described in the previous paper 3.3.

Reference: 1. Smeds S, Peter HJ, Jörtsö E, Gerber H, Studer H. Naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of mouse thyroids. Cancer Res. 1987;47:1646-51.2. Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: the basis for understanding thyroid function and nodular goiter growth. Endocr Rev. 1989;10:125–35. doi: 10.1210/edrv-10-2-125.3. Marelli F, Rurale G, Persani L. From Endoderm to Progenitors: An Update on the Early Steps of Thyroid Morphogenesis in the Zebrafish. Front Endocrinol (Lausanne). 2021;12:664557. doi: 10.3389/fendo.2021.664557.

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