Figure 2.TM4SF1 marks senescent β-cells in mice. (A) Immunostaining for TM4SF1 and nuclear exclusion of HMGB1 in mouse β-cells. (B) Scatter plot showing a negative relationship between TM4SF1 protein levels and nuclear HMGB1 in mouse islets. TM4SF1 levels negatively correlated with nuclear-to-cytoplasmic HMGB1 ratio (p < 0.0001), correlating higher TM4SF1 expression with HMGB1 nuclear exclusion. Protein levels were quantified as mean fluorescence intensity (MFI). n=3 Control, n=3 HFD, n=3HFD + Bcl2i. 10-13 images per animal were analyzed. (C–E) Islets isolated from 7-8-month-old C57Bl/6J male retired breeders were FACS sorted into non-senescent (β-Gal negative) and senescent (β-Gal positive) subpopulations for RNA-seq after gating for enrichment of β-cells (GSE121539). Individual matched subpopulations from β-Gal negative and positive from 7 biological replicates. Specific gene expression was compared between senescent and non-senescent populations: Cdkn1a, Plaur and Tm4sf1.
