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Expression profiling of a human endocrine pancreas iPSC model

Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to the endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. “insulin secretion”; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.

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Human Endocrine Pancreas iPSC Model Data Access Agreement

This agreement governs the terms on which access will be granted to the RNA-sequencing data generated as part of the “Characterization of a human iPSC-derived endocrine pancreas model” study. In signing this agreement, You are agreeing to be bound by the terms and conditions of access set out in this agreement. For the sake of clarity, the terms of access set out in this agreement apply both to the User and the User’s Institution (as defined below). User Institution and User are referred to within the agreement as “You” and “Your” shall be construed accordingly. Definitions: Investigators means the group of investigators based in Oxford, UK, which have generated the Data as part of the STEMBANCC consortium. Data means all and any human genetic data obtained from the Investigators. Data Subject means a person, who has been informed of the purpose for which the Data is held and has given his/her informed consent thereto. User means a researcher whose User Institution has previously completed this Data Access Agreement and has received acknowledgement of its acceptance. Publications means, without limitation, articles published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research. User Institution means the organisation at which the User is employed, affiliated or enrolled. Terms and Conditions: In signing this Agreement: 1. You agree to use the Data only for the advancement of medical research, according to the consent obtained from sample donors. 2. You agree not to use the Data or any part thereof for the creation of products for sale or for any commercial purpose. 3. You agree to preserve, at all times, the confidentiality of information and Data pertaining to Data Subjects. In particular, You undertake not to use, or attempt to use the Data to compromise or otherwise infringe the confidentiality of information on Data Subjects and their right to privacy. 4. You agree not to attempt to link the data provided under this agreement to other information or archive data available for the data sets provided, even if access to that data has been formally granted to you, or it is freely available without restriction, without specific permission being sought from the relevant access committees. 5. You agree not to transfer or disclose the Data, in whole or part, or any identifiable material derived from the Data, to others, except as necessary for data/safety monitoring or programme management. Should You wish to share the Data with a collaborator outside the same Institution, the third party must make a separate application for access to the Data. 6. You agree to use the data for the approved purpose and project described in your application; use of the data for a new purpose or project will require a new application and approval. 7. You agree to acknowledge in any work based in whole or part on the Data, the published paper from which the Data derives as well as the StemBANCC project which generated the Data. The phrasing “Data used in this manuscript has received funding from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement number 115439 (StemBANCC), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution.” should be used for acknowledging the STEMBANCC project. 8. You accept that the Investigators, the original data creators, depositors or copyright holders, or the funders of the Data or any part of the Data supplied: a. bear no legal responsibility for the accuracy or comprehensiveness of the Data; and b. accept no liability for indirect, consequential, or incidental, damages or losses arising from use of the Data, or from the unavailability of, or break in access to, the Data for whatever reason. 9. You understand and acknowledge that the Data is protected by copyright and other intellectual property rights, and that duplication, except as reasonably required to carry out Your research with the Data, or sale of all or part of the Data on any media is not permitted. 10. You recognise that nothing in this agreement shall operate to transfer to the User Institution any intellectual property rights relating to the Data. The User Institution has the right to develop intellectual property based on comparisons with their own data. 11. You accept that this agreement will terminate immediately upon any breach of this agreement by You and You will be required to destroy any Data held. 12. You accept that it may be necessary for the Investigators or its appointed agent to alter the terms of this agreement from time to time in order to address new concerns. In this event, the Investigators or its appointed agent will contact You to inform You of any changes and You agree that Your continued use of the Data shall be dependent on the parties entering into a new version of the Agreement. 13. You accept that the Data is protected by and subject to international laws, including but not limited to the UK Data Protection Act 1998, and that You are responsible for ensuring compliance with any such applicable law. The Oxford Human Islet Data Access Committee reserves the right to request and inspect data security and management documentation to ensure the adequacy of data protection measures in countries that have no national laws comparable to that which pertain in the EAA. 14. This agreement shall be construed, interpreted and governed by the laws of England and Wales and shall be subject to the non-exclusive jurisdiction of the English courts.

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001001803 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00001194667 bam 9.6 GB
EGAF00001194668 bam 9.7 GB
EGAF00001194669 bam 10.1 GB
EGAF00001194670 bam 10.0 GB
EGAF00001194671 bam 9.3 GB
EGAF00001194672 bam 8.5 GB
EGAF00001194673 bam 10.4 GB
EGAF00001194674 bam 9.7 GB
EGAF00001194675 bam 9.9 GB
EGAF00001194676 bam 7.0 GB
EGAF00001194677 bam 11.5 GB
EGAF00001194678 bam 11.2 GB
12 Files (116.8 GB)