T2D Pancreatic Fibroblast SERPINF1-NR2F2 Axis
Huang et al. 2022 analyzed scRNA-seq from pancreatic islets (E-MTAB-5061) and found:
Key Finding
SERPINF1 is predominantly expressed in pancreatic fibroblasts, with higher expression in healthy donors than in T2D donors. A higher proportion of SERPINF1-high fibroblasts was present in healthy tissue.
GSVA Pathway Analysis
SERPINF1-high fibroblasts showed activation of:
- PI3K-AKT signaling
- Interferon-α response
- Reactive oxygen species pathway
- Angiogenesis, WNT-β-catenin signaling
SERPINF1-low fibroblasts showed activation of:
- Apoptosis
- Inflammatory response
- Myogenesis
- Complement, coagulation
Transcription Factor Regulation
SCENIC analysis identified:
- NR2F2 (nuclear receptor subfamily 2, group F, member 2) — specific TF in SERPINF1-high fibroblasts.
- NFE2L2 — specific TF in SERPINF1-low fibroblasts (anti-oxidation and inflammation regulator).
- 9 shared TFs between groups: HEYL, HOXB2, HOXA1, ATF5, ZNF467, SMARCB1, CREB3L1, JUNB, NR1H2.
NR2F2 regulated 18 genes that overlapped with T2D DEGs; 4 target genes (SERPINF1, SFRP4, CELA3A, CTRC) were differentially expressed between SERPINF1-high and SERPINF1-low fibroblasts.
Significance
This proposes a fibroblast-specific regulatory mechanism in T2D pancreatic islets, where reduced SERPINF1 and altered NR2F2 activity may contribute to islet pathology. The role of NR2F2 in diabetes pathogenesis requires further study.