Molecules with effects on cellular development and function

A method of identifying candidate molecular mediators of parenchymal and nonparenchymal cell interactions, comprising:

• (a) obtaining a first co-culture of a parenchymal cell population and a first non-parenchymal cell population, measuring a tissue-specific function of the parenchymal cells and correlating the tissue-specific function with an inductive ability of the first non-parenchymal cell population;
• (b) obtaining a second co-culture of the parenchymal cell population and a second non-parenchymal cell population, measuring the tissue-specific function of the parenchymal cells and correlating the tissue-specific function with an inductive ability of the second non-parenchymal cell population;
• (c) obtaining a third co-culture of the parenchymal cell population and a third non-parenchymal cell population, measuring the tissue-specific function of the parenchymal cells and correlating the tissue-specific function with an inductive ability of the third non-parenchymal cell population;
• (d) identifying changes in the tissue-specific function resulting from co-culture of the parenchymal cell population with the first, second and third non-parenchymal cell populations;
• (e) generating a functional profile, comprising:
• (i) identifying a first gene expression profile of a culture of the first non-parenchymal cell population, a second gene expression profile of a culture of the second non-parenchymal cell population, and a third gene expression profile of a culture of the third non-parenchymal cell population;
• (ii) comparing the first, second, and third gene expression profiles to identify a plurality of genes differentially expressed when comparing the profiles;
• and
• (iii) correlating the differential expression of the plurality of genes with the changes in the tissue- specific function;
• wherein the functional profile comprises the plurality of genes differentially expressed and identifies the genes as candidate molecular mediators,
• wherein the non-parenchymal cell populations comprise fibroblast cells and wherein the parenchymal cell population comprises hepatocytes, and wherein the fibroblast cells are a cell line selected from the group consisting of 3T3-J2 fibroblasts, mouse embryonic fibroblasts, and NIH-3T3 fibroblasts, and
• wherein the functional profile comprises genes selected from the group consisting of Delta-like 1 homolog;
• Endothelial differentiation, sphingolipid G-protein-coupled receptor, 3;
• Aquaporin 1;
• T-cadherin (Cdh13);
• vascular cadherin-2;
• tight junction protein2;
• Insulin-like growth factor II (IGF-II);
• Connective tissue growth factor;
• Follistatin:
• Secreted phosphoprotein 1;
• C-fos induced growth factor (VEGF-D);
• Small inducible cytokine A9;
• Ceruloplasmin:
• Adiponectin (Acrp30);
• fibroblast inducible secreted protein;
• osteoblast specific factor 2 (fasciclin I-like);
• Mouse insulin-like growth factor II (IGF-II);
• Tnf receptor associated factor 4 (Traf4);
• apolipoprotein D;
• Haptoglobin;
• Follistatin;
• Interleukin-6;
• Connective Tissue Growth Factor;
• small inducible cytokine B subfamily, member 5(Scyb5);
• Decorin;
• laminin alpha 4 chain;
• Jun-B oncogene;
• Early growth response 1;
• Notch gene homolog 1 (Drosophila);
• FBJ osteosarcoma oncogene;
• Interferon regulatory factor 1;
• 204 interferon-activatable protein;
• Splicing factor, arginine/serine-rich 3;
• Heterogeneous nuclear ribonucleoprotein D-like protein JKTBP;
• Autoantigen la (ss-b);
• High mobility group box 1;
• DNA polymerase delta small subunit (pold2);
• Esk kinase;
• Mouse dihydrofolate reductase gene:
• 3′ end;
• Pm 1 protein;
• B-cell translocation gene 2;
• Thymidine kinase 1;
• Shc SH2-domain binding protein 1;
• Guanylate nucleotide binding protein 4;
• Interferon-induced protein 44;
• Spindle pole body component 25 homolog;
• Baculoviral IAP repeat-containing 5;
• Aurora kinase A;
• Solute carrier family 1 (glial high affinity glutamate transporter), member 3;
• Leucine rich repeat containing 17;
• Interferon, alpha-inducible protein;
• Minichromosome maintenance deficient 5, cell division cycle 46;
• Cysteine rich protein 61;
• Apolipoprotein D;
• Interferon-induced protein with tetratricopeptide repeats 3;
• Interferon-induced protein with tetratricopeptide repeats 1;
• 2′-5′ oligoadenylate synthetase-like 2;
• fidgetin-like 1;
• Rac gtpase-activating protein 1;
• and Translocase of inner mitochondrial membrane 8 homolog a.