Pancreatic and intestinal endocrine cells in zebrafish share common transcriptomic signatures and regulatory programmes
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RESEARCH ARTICLE
Open Access
Pancreatic and intestinal endocrine cells in zebrafish share common transcriptomic signatures and regulatory programmes Arnaud Lavergne1†, Estefania Tarifeño-Saldivia1,2†, Justine Pirson1, Anne-Sophie Reuter1, Lydie Flasse1, Isabelle Manfroid1, Marianne L. Voz1*† and Bernard Peers1*†
Abstract Background: Endocrine cells of the zebrafish digestive system play an important role in regulating metabolism and include pancreatic endocrine cells (PECs) clustered in the islets of Langerhans and the enteroendocrine cells (EECs) scattered in the intestinal epithelium. Despite EECs and PECs are being located in distinct organs, their differentiation involves shared molecular mechanisms and transcription factors. However, their degree of relatedness remains unexplored. In this study, we investigated comprehensively the similarity of EECs and PECs by defining their transcriptomic landscape and comparing the regulatory programmes controlled by Pax6b, a key player in both EEC and PEC differentiations. Results: RNA sequencing was performed on EECs and PECs isolated from wild-type and pax6b mutant zebrafish. Data mining of wild-type zebrafish EEC data confirmed the expression of orthologues for most known mammalian EEC hormones, but also revealed the expression of three additional neuropeptide hormones (Proenkephalin-a, Calcitonin-a and Adcyap1a) not previously reported to be expressed by EECs in any species. Comparison of transcriptomes from EECs, PECs and other zebrafish tissues highlights a very close similarity between EECs and PECs, with more than 70% of genes being expressed in both endocrine cell types. Comparison of Pax6b-regulated genes in EECs and PECs revealed a significant overlap. pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. Finally, we show that the homeodomain of Pax6b is dispensable for its action in both EECs and PECs. (Continued on next page)
* Correspondence: [email protected]; [email protected] † Marianne L. Voz and Bernard Peers are co-last authors and corresponding authors. † Arnaud Lavergne and Estefania Tarifeño-Saldivia are co-first authors. 1 Laboratory of Zebrafish Development and Disease Models (ZDDM), GIGA, University of Liège, Avenue de l’Hôpital 1, B34, Sart Tilman, 4000 Liège, Belgium Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other th
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