Predicting the Key Regulators of Cell Identity in Human Adult Pancreas

• DOI: 10.1101/2020.09.23.310094
• Publication Date: 2020-09-26T04:55:12Z
• Authors: Lotte Vanheer; Federica Fantuzzi; San Kit To; Andrea Alex Schiavo; Matthias Van Haele; Tine Haesen; Xiaoyan Yi; Adrian Janiszewski; Joel Chappell; Adrien Rihoux; Toshiaki Sawatani; Tania Roskams; Francois Pattou; Julie Kerr-Conte; Miriam Cnop; Vincent Pasque
• Keywords: PDX1; Gene regulatory network; PAX6; Cell type

SUMMARY Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, and networks underlying cellular in human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA-sequencing datasets pancreas, totaling 7393 cells, comprehensively reconstruct We show a network 142 forms distinct modules characterize pancreatic cell types. present evidence our approach identifies regulators pancreas. predict HEYL, BHLHE41 JUND are active acinar, beta alpha respectively, these proteins as well induced pluripotent stem (hiPSC)-derived islet cells. Using transcriptomics, found represses genes hiPSC-alpha Both depletion seemed to increase number sc-enterochromaffin cells hiPSC-derived islets. The comprehensive atlas can be explored interactively online. anticipate analysis starting point for more sophisticated dissection how regulate Furthermore, given major embryo often perturbed diseases, understanding work will relevant disease. HIGHLIGHTS Reconstruction types An interactive resource explore visualize expression states Prediction putative drive primary islets induces apoptosis