Inferring regulators of cell identity in the human adult pancreas

Abstract Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multi...

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Bibliographic Details
Published in:	NAR genomics and bioinformatics Vol. 5; no. 3; p. lqad068
Main Authors:	Vanheer, Lotte, Fantuzzi, Federica, To, San Kit, Schiavo, Andrea, Van Haele, Matthias, Ostyn, Tessa, Haesen, Tine, Yi, Xiaoyan, Janiszewski, Adrian, Chappell, Joel, Rihoux, Adrien, Sawatani, Toshiaki, Roskams, Tania, Pattou, Francois, Kerr-Conte, Julie, Cnop, Miriam, Pasque, Vincent
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-09-2023
Online Access:	Get full text
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Summary:	Abstract Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA-sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies regulators of cell identity and cell states in the human adult pancreas. We predict that HEYL, BHLHE41 and JUND are active in acinar, beta and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell (hiPSC)-derived islet cells. Using single-cell transcriptomics, we found that JUND represses beta cell genes in hiPSC-alpha cells. BHLHE41 depletion induced apoptosis in primary pancreatic islets. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity and cell states in the human adult pancreas. Graphical Abstract Graphical Abstract
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Lead contact. The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
ISSN:	2631-9268 2631-9268
DOI:	10.1093/nargab/lqad068