Identification of distinct functions of GLIS3 in β-cell generation critical to prevention of neonatal diabetes
Scoville, D. W.; Grimm, S. A.; Xu, X.; Anchang, B.; Jetten, A. M.
Show abstract
GLIS3 plays a critical role in pancreatic {beta} cells and diabetes, being one of only a few genes implicated in Type 1, Type 2, and Gestational diabetes. In addition to {beta} cells, GLIS3 is expressed embryonically in bipotent and proendocrine progenitor cells, suggesting a role in endocrine lineage development in mice. We hypothesize that GLIS3 is playing important roles in endocrine development as well as during {beta} cell differentiation. We utilized single cell RNA-sequencing at three different timepoints (embryonic day (e)13.5, e15.5, and e18.5) and single nucleus (sn)ATAC-sequencing at e15.5 in both wild type (WT) and Glis3 Knockout (Glis3KO) mouse embryos. This analysis revealed that the numbers of bipotent, proendocrine progenitor, and all subsequent endocrine cells were proportionately reduced in Glis3KO mice. Additionally, loss of GLIS3 function generates a unique subpopulation of cells that fail to upregulate Ins2 transcription and downregulate expression of several ribosomal and oxidative phosphorylation genes normally repressed during pre{beta} to {beta} cell differentiation. Our study therefore shows that GLIS3 regulates two distinct stages: the embryonic generation/differentiation of bipotent cells and the differentiation of pre{beta} to {beta} cells. Dysregulation of these two stages provides a causal mechanism for the development of neonatal diabetes in GLIS3-deficiency.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Glucose-dependent miR-125b is a negative regulator of β-cell function 96%
- Pancreatic β-cell specific loss of E2f1 impairs insulin secretion and β-cell identity through the epigenetic repression of non β-cell programs 95%
- An integrated map of cell type-specific gene expression in pancreatic islets 95%
Similar papers in this journal
- Generation and validation of an aryl hydrocarbon receptor knockout human embryonic stem cell line 95%
- β-Hydroxybutyrate promotes basal insulin secretion while decreasing glucagon secretion in mouse and human islets. 93%
- The Cardiolipin Transacylase Tafazzin Regulates Basal Insulin Secretion and Mitochondrial Function in Pancreatic Islets from Mice 93%
Similar papers in this journal
- Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners 96%
- Physically interacting beta-delta pairs in the regenerating pancreas revealed by single cell sequencing 95%
- Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs 95%
Similar papers in this journal
- Generation and application of novel hES cell reporter lines for the differentiation and maturation of hPS cell-derived islet-like clusters 95%
- Neuropeptide Neuromedin B does not alter body weight and glucose homeostasis nor does it act as an insulin-releasing peptide 94%
- Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans 94%
Similar papers in this journal
- Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene 95%
- Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry 94%
- Target deconvolution of an insulin hypersecretion-inducer acting through VDAC1 with a distinct transcriptomic signature in beta-cells 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.