Fig. 2. Highly concentrated trehalose-induced signaling pathways detected in human fibroblasts by whole transcriptome analysis with RNA-seq.

a The heatmap shows the z-scores of the gene expression downregulated in 2D and 3D fibroblasts by trehalose treatment for 24 and 72 h, respectively. b The Venn diagram demonstrates the numbers of downregulated genes. The 131 genes downregulated in 2D and 3D fibroblasts were used for an Ingenuity pathway analysis (IPA). c Canonical pathways detected in IPA using the genes downregulated by trehalose were shown together with the number of genes involved in the detected pathway. d Upstream factors of the downregulated genes by trehalose were indicated together with the number of genes involved in the detected factor. The upstream factors signaling by activation or by inhibition were shown in brown or blue, respectively. e A network demonstrates the interaction of CDKN1A, which was detected as an upstream factor of the downregulated genes, and the signals inhibited by trehalose, which are shown as blue lines. The green shapes indicate the genes downregulated by trehalose. f A heatmap shows the z-scores of the gene expressions upregulated in 2D and 3D fibroblasts by trehalose. g The Venn diagram demonstrates the numbers of the upregulated genes. h Canonical pathways detected in IPA using the genes upregulated by trehalose were shown together with the number of genes involved in the detected pathway. i Upstream factors of the upregulated genes by trehalose were indicated together with the number of genes involved in the detected factors. The upstream factors signaling by activation or by inhibition were shown in brown or blue, respectively. j A network demonstrates the interaction of AURK, detected as an upstream factor of the downregulated genes, and the factors predicted to activate interaction with AURK by trehalose, which are shown as red lines. The red shapes indicate the genes upregulated by trehalose.