Multidimensional analysis and therapeutic development using patient iPSC–derived disease models of Wolfram syndrome

Abstract

Conflict of interest:FU is an inventor of 3 patents related to Wolfram syndrome treatment, US 9,891,231 "Soluble MANF in pancreatic beta-cell disorders, " and US 10,441,574 and US 10,695,324 "Treatment for Wolfram syndrome and other endoplasmic reticulum stress disorders. " JRM is an inventor on a patent and patent application relating to stem cell-derived pancreatic islets, US 10,030,229 "SC-β cells and compositions and methods for generating the same" and US application PCT/US2019/032643 "Methods and Compositions for Generating Cells of Endodermal Lineage and Beta Cells and Uses Thereof. " FU is a founder and president of CURE4WOLFRAM, Inc. JRM is a consultant for Sana Biotechnology. JC and JK are co-CEOs of and report personal fees from and equity holdings in Amylyx Pharmaceuticals Inc. JC and JK have 2 patents, "Compositions for improving cell viability and methods of use thereof" (US 9,872,865; US Patent 10,251,896; AU 2014242123; EP 14775675.3; and JP2016515575A) and "For improving the composition of cell viability and using the method for the composition" (CN105050593B), issued to Amylyx Pharmaceuticals Inc. JL reports personal fees from and equity holdings in Amylyx Pharmaceuticals Inc.

Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells

“…A universal definition of β-cell identity would not only serve as a useful resource in research, but also a potentially important attribute of cells to be used for therapy [ 23 ]. This can be particularly difficult in SC-islets, as SC-β cell identity can lack distinctiveness compared to other cell types in the tissue, particularly the SC-EC cells [ 8 , 10 , 24 ]. To establish a universal definition of healthy β-cell identity, we identified genes enriched in β-cells compared to all other endocrine cells and highlighted the genes whose expression is shared across all tissue sources (Fig.…”

Comparative and Integrative Single Cell Analysis Reveals New Insights into the Transcriptional Immaturity of Stem Cell-Derived β Cells

“…A universal definition of β-cell identity would not only serve as a useful resource in research, but also a potentially important attribute of cells to be used for therapy 23 . This can be particularly difficult in SC-islets, as SC-β cell identity can lack distinctiveness compared to other cell types in the tissue, particularly the SC-EC cells 8,10,24 . To establish a universal definition of healthy β-cell identity, we identified genes enriched in β-cells compared to all other endocrine cells and identified the genes whose expression is shared across all tissue sources (Fig.…”

The hope, hype and obstacles surrounding cell therapy

“…In this case, iPSCs are more used to create disease research models than therapies. 80 In other cases, pathophysiological changes may begin in the earliest stages of life, leading to irreversible malfunctions. Ciliopathy is a good example of a disease in which a mutated gene is expressed in almost all cells.…”