CC founder strains: body weight CC founder strains: glucose during oGTTs CC founder strains: insulin during oGTTs CC founder strains: glucose during ITTs Co-expression gene modules in F2 islets ~33,000 transcripts ~20,500 in modules “cell cycle” (184 transcripts) Module enrichments by GO module GO GO.term black blue brown cyan darkgreen darkgrey darkred darkturquoise green greenyellow grey60 lightcyan lightgreen lightgreen lightgreen lightgreen lightgreen lightgreen lightyellow magenta midnightblue orange pink purple red royalblue salmon tan turquoise yellow BP BP BP CC BP CC BP BP CC MF BP BP BP BP BP BP BP BP BP BP BP BP BP BP CC BP CC MF MF BP positive regulation of T cell cytokine production chromatin modification fructose 1,6-bisphosphate metabolic process mitochondrial respiratory chain complex I carbon dioxide transport polysome fructose 2,6-bisphosphate metabolic process adiponectin-mediated signaling pathway proton-transporting V-type ATPase, V1 domain chemokine activity antigen processing and presentation of endogenous peptide antigen via MHC class I translational elongation nuclear division mitosis M phase of mitotic cell cycle M phase organelle fission cell cycle phase neutrophil mediated immunity maternal process involved in female pregnancy regulation of lipoprotein metabolic process NAD metabolic process detection of light stimulus involved in visual perception otic vesicle formation organellar large ribosomal subunit DNA replication, synthesis of RNA primer zymogen granule membrane extracellular matrix structural constituent neuropeptide hormone activity RNA splicing p.value 0.00000184 6.88E-18 8.16E-08 4.32E-111 1.62E-40 3.67E-58 2.42E-14 4.59E-37 5.69E-15 1.09E-32 8.72E-25 1.89E-59 1.39E-218 1.39E-218 3.46E-212 2.36E-211 3.92E-206 2.22E-178 3.14E-21 9.65E-11 5.24E-09 1.41E-27 9.20E-16 9.39E-25 1.57E-15 8.40E-33 4.45E-49 5.44E-86 0.00000139 2.06E-15 Module enrichments by KEGG module KEGG.name black blue brown cyan darkgreen darkgrey darkred darkturquoise green greenyellow grey60 lightcyan lightgreen lightgreen lightgreen lightgreen lightgreen lightgreen lightyellow magenta midnightblue orange pink purple red royalblue salmon tan turquoise yellow Ascorbate and aldarate metabolism Lysosome PPAR signaling pathway Parkinson's disease Bile secretion Ribosome Glycosaminoglycan biosynthesis - chondroitin sulfate Type II diabetes mellitus SNARE interactions in vesicular transport NOD-like receptor signaling pathway Proteasome Ribosome Cell cycle DNA replication Oocyte meiosis Mismatch repair Progesterone-mediated oocyte maturation Homologous recombination Dorso-ventral axis formation Bile secretion Pantothenate and CoA biosynthesis Glycosaminoglycan degradation MAPK signaling pathway Thyroid cancer Ubiquinone and other terpenoid-quinone biosynthesis Spliceosome Pancreatic secretion ECM-receptor interaction Neuroactive ligand-receptor interaction Ubiquitin mediated proteolysis p.value 0.0000481 5.73E-15 8.09E-08 3.20E-54 8.50E-10 9.98E-29 0.000148 0.00000609 0.0000185 6.52E-22 0.000000172 1.56E-75 6.76E-80 3.94E-65 7.49E-22 1.63E-18 1.22E-17 7.98E-16 9.63E-12 0.000983 2.16E-13 8.15E-16 0.00133 7.29E-08 0.00000085 2.40E-08 6.03E-39 9.15E-36 0.000207 1.46E-08 % variance explained by module eigengenes 0.6 0.5 0.4 0.3 0.2 0.1 0 Architecture of module eigengenes Architecture of MElightgreen and islet D2O incorporation Correlation between MEs and all clinical traits Correlation between MEs and all clinical traits Correlation between MEs and all clinical traits Search for circulating molecules stimulating b-cell replication Properties of candidates: Secreted factors Correlated to islet D2O Located at cell cycle loci e.g., Igfals in adipose - secreted - correl to islet D2O = 0.48 - correl to insulin = 0.58 - cis eQTL on Chr17 - coding SNP (Sanger) Igfals KO mice Igfals expression in our database: Are circulating IGF levels different?
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