|  Help  |  About  |  Contact Us

HT Experiment :

Experiment Id  GSE78966 Series Id  E-GEOD-78966
Name  Progenitor Cell Marker Aldehyde Dehydrogenase 1a3 Defines a Subset of Failing Pancreatic Beta Cells in Diabetic Mice Experiment Type  RNA-Seq
Study Type  WT vs. Mutant Source  GEO
Curation Date  2023-08-09
description  Insulin-producing beta cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, sets the stage for progression from beta cell dysfunction to beta cell dedifferentiation. In this study, we sought to isolate and functionally characterize failing beta cells, as a preliminary step to identify pathways to reverse dedifferentiation. Using various experimental models of diabetes, we found a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH+) as beta cells become dedifferentiated. Flow-sorted ALDH+ islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH+ cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV, and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of beta cell failure. RNA-Sequencing analysis of 2 different cell types in 2 different genotype categories.
  • variables:
  • cell type,
  • bulk RNA-seq,
  • genotype

1 Publications

Trail: HTExperiment

15 Samples

Trail: HTExperiment