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| Status |
Public on Aug 01, 2020 |
| Title |
Pancreatic and intestinal endocrine cells share common transcriptomic signatures and gene regulatory networks |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Endocrine cells of the digestive system, including the pancreatic endocrine cells (PECs) clustered in the islets of Langerhans and the enteroendocrine cells (EECs) scattered in the intestinal epithelium, play an important role in metabolism. Although EECs and PECs are located in distinct organs, they share many features and several common genes control their differentiation. In this study, we investigated comprehensively the similarity of EECs and PECs by defining their transcriptomic landscape and comparing the regulatory networks controlled by pax6b, a key player in both EECs and PECs.
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 orthologs for most known mammalian EEC hormones but also revealed the expression of three additional neuropeptide hormones (Proenkephalin-a, Calcitonin-a and Adcyap1a) not yet 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 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.
Conclusion: This study highlights the close relatedness of EECs and PECs at the transcriptomic and regulatory levels, supporting the hypothesis of a common phylogenetic origin and underscoring the potential implication of EECs in metabolic diseases such as Type 2 diabetes.
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| Overall design |
RNA-sequencing of 13 samples. Pancreatic endocrine cell (pax6b:GFP +) transcriptomic profiles of 27 hpf (hours post fertilization) wild type (WT) and pax6b-/- (MUT) zebrafish embryos were generated in triplicates. Enteroendocrine cell (pax6b:GFP +) transcriptomic profiles of 4d wild type (WT) and pax6b-/- (MUT) zebrafish emryos were generated in 4 replicates and 3 replicates, respectively.
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| Contributor(s) |
Lavergne A, Tarifeño-Saldivia E, Pirson J, Reuter A, Manfroid I, Voz ML, Peers B |
| Citation(s) |
32867764, 35286299 |
| Submission date |
Apr 21, 2020 |
| Last update date |
Apr 06, 2022 |
| Contact name |
Arnaud Lavergne |
| Organization name |
University of Liège
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| Department |
GIGA
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| Street address |
Avenue de l'hôpital 11
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| City |
Liège |
| State/province |
Liège |
| ZIP/Postal code |
4000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA627266 |
| SRA |
SRP257811 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149081_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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