RT Journal Article SR Electronic T1 Single-cell transcriptome analysis reveals cell-cell communication and thyrocyte diversity in the zebrafish thyroid gland JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.13.891630 DO 10.1101/2020.01.13.891630 A1 Pierre Gillotay A1 Meghna Shankar A1 Benoit Haerlingen A1 Sema Elif Eski A1 Macarena Pozo-Morales A1 Inés Garteizgogeascoa Suñer A1 Susanne Reinhardt A1 Annekathrin Kränkel A1 Juliane Bläsche A1 Andreas Petzold A1 Nikolay Ninov A1 Gokul Kesavan A1 Christian Lange A1 Michael Brand A1 Vincent Detours A1 Sabine Costagliola A1 Sumeet Pal Singh YR 2020 UL http://biorxiv.org/content/early/2020/03/27/2020.01.13.891630.abstract AB The thyroid gland regulates growth and metabolism via production of thyroid hormone in follicles composed of thyrocytes. So far, thyrocytes have been assumed to be a homogenous population. To uncover genetic heterogeneity in the thyrocyte population, and molecularly characterize the non-thyrocyte cells surrounding the follicle, we developed a single-cell transcriptome atlas of the zebrafish thyroid gland. The 6249-cell atlas includes profiles of thyrocytes, blood vessels, lymphatic vessels, immune cells and fibroblasts. Further, the thyrocytes could be split into two sub-populations with unique transcriptional signature, including differential expression of the transcription factor pax2a. To validate thyrocyte heterogeneity, we generated a CRISPR/Cas9-based pax2a knock-in line, which demonstrated specific pax2a expression in the thyrocytes. However, a population of pax2a-low mature thyrocytes interspersed within individual follicles could be distinguished, corroborating heterogeneity within the thyrocyte population. Our results identify and validate transcriptional differences within the nominally homogenous thyrocyte population.One-line summary Single-cell analysis uncovers latent heterogeneity in thyroid follicular cells.