Extended Data Fig. 7: A Cluster of ARC DEGs Correlates with Changing Bone Mass in Female Esr1Nkx2.1-Cre Mutants.

a, Heatmaps of top 50 DEGs listed to the right following analyses of bulk RNA-Seq datasets of Esr1fl/fl and Esr1Nkx2.1-Cre age-matched female littermates maintained on standard breeder chow (SD) or high-fat diet (HFD) for 17 weeks starting at 10 weeks of age; samples include microdissected ARC (left panel), whole pituitary glands (middle panel) or liver tissue (right panel). The cluster of secreted proteins/peptides for the ARC attenuated by HFD are highlighted in red text. Legend for each heatmap shows relative Z-Scores. b, Normalized reads for candidate genes from the ARC; Penk in pituitary with either SD or HFD (N = 2–4). c, Relative expression of transcripts as listed in the female hypothalamus at 2.5 weeks of age shown in bar graphs with individual points (N = 4–8). d, Relative expression of transcripts in microdissected ARC harvested from control Esr1fl/fl and mutant Esr1Nkx2.1-Cre age-matched females (red) or males (blue), (N = 2–5). e, CCN3 (green) expression in the posterior ARC of mutant female, control virgin female and control intact male. Scale bars = 100 µm. One-Way ANOVA for panel b, Unpaired Student’s T-test 2-tailed for panels c and d, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = not significant. ns = not significant. Error Bars ± SEM. Abbreviations: ARC arcuate nucleus. ME median eminence.