Author:
Schmidt Mason D.,Ishahak Matthew,Augsornworawat Punn,Millman Jeffrey R.
Abstract
AbstractDiabetes cell replacement therapy has the potential to be transformed by human pluripotent stem cell-derived β cells (SC-β cells). However, the precise identity of SC-β cells in relationship to primary fetal and adult β-cells remains unclear. Here, we used single-cell sequencing datasets to characterize the transcriptional identity of islets from in vitro differentiation, fetal islets, and adult islets. Our analysis revealed that SC-β cells share a core β-cell transcriptional identity with human adult and fetal β-cells, however SC-β cells possess a unique transcriptional profile characterized by the persistent expression and activation of progenitor and neural-biased gene networks. These networks are present in SC-β cells, irrespective of the derivation protocol used. Notably, fetal β-cells also exhibit this neural signature at the transcriptional level. Our findings offer insights into the transcriptional identity of SC-β cells and underscore the need for further investigation of the role of neural transcriptional networks in their development.
Funder
Washington University School of Medicine in St. Louis
National Institute of Diabetes and Digestive and Kidney Diseases
Juvenile Diabetes Research Foundation United States of America
Edward Mallinckrodt, Jr. Foundation
Publisher
Springer Science and Business Media LLC