1. Analysis of Differentiation Protocols Defines a Common Pancreatic Progenitor Molecular Signature and Guides Refinement of Endocrine Differentiation.
- Author
-
Wesolowska-Andersen A, Jensen RR, Alcántara MP, Beer NL, Duff C, Nylander V, Gosden M, Witty L, Bowden R, McCarthy MI, Hansson M, Gloyn AL, and Honore C
- Subjects
- Biomarkers, Cell Culture Techniques, Cells, Cultured, Chromatin Assembly and Disassembly genetics, Computational Biology methods, Epigenesis, Genetic, Gene Expression Profiling, Humans, Immunophenotyping, Islets of Langerhans cytology, Cell Differentiation, Pancreas cytology, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism
- Abstract
Several distinct differentiation protocols for deriving pancreatic progenitors (PPs) from human pluripotent stem cells have been described, but it remains to be shown how similar the PPs are across protocols and how well they resemble their in vivo counterparts. Here, we evaluated three differentiation protocols, performed RNA and assay for transposase-accessible chromatin using sequencing on isolated PPs derived with these, and compared them with fetal human pancreas populations. This enabled us to define a shared transcriptional and epigenomic signature of the PPs, including several genes not previously implicated in pancreas development. Furthermore, we identified a significant and previously unappreciated cross-protocol variation of the PPs through multi-omics analysis and demonstrate how such information can be applied to refine differentiation protocols for derivation of insulin-producing beta-like cells. Together, our study highlights the importance of a detailed characterization of defined cell populations derived from distinct differentiation protocols and provides a valuable resource for exploring human pancreatic development., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF