TY  - JOUR
A1  - Aga-Barfknecht, Heja
A1  - Soultoukis, George A.
A1  - Stadion, Mandy
A1  - Garcia-Carrizo, Francisco
A1  - Jähnert, Markus
A1  - Gottmann, Pascal
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schürmann, Annette
T1  - Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue
JF  - International journal of molecular sciences
N2  - Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.
KW  - MSCs
KW  - fatty pancreas
KW  - WAT
KW  - lineage commitment
KW  - transcriptomics
KW  - miRNAs
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23042108
SN  - 1422-0067
VL  - 23
IS  - 4
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Jonas, Wenke
A1  - Kluth, Oliver
A1  - Helms, Anett
A1  - Voss, Sarah
A1  - Jahnert, Markus
A1  - Gottmann, Pascal
A1  - Speckmann, Thilo
A1  - Knebel, Birgit
A1  - Chadt, Alexandra
A1  - Al-Hasani, Hadi
A1  - Schürmann, Annette
A1  - Vogel, Heike
T1  - Identification of novel genes involved in hyperglycemia in mice
JF  - International journal of molecular sciences
N2  - Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. 
Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. 
Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. 
Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MINE cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting beta-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.
KW  - beta-cell
KW  - diabetes
KW  - proliferation
KW  - apoptosis
KW  - QTL
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23063205
SN  - 1661-6596
SN  - 1422-0067
VL  - 23
IS  - 6
PB  - MDPI
CY  - Basel
ER  -