Fig. 4.

Dynamics of perturbed functional clusters in T21 neural lines based on integrated analysis of data from NPCs and DiffNPCs. Eleven deficient functional clusters were identified based on annotations using DAVID considering all transcriptome and proteome data sets from NPCs and DiffNPCs, respectively. Fold enrichment of clusters was obtained from separate data analysis of NPCs and DiffNPCs, respectively. The clusters were named after representative annotations. Five dysregulated clusters (DNA replication, pluripotency, synapse, neuronal and collagen) were characteristic for trisomic NPCs suggesting a significant impact of these clusters in early T21 neurogenesis. In DiffNPCs, three dysregulated clusters are distinguished (TGF-beta signaling, oxidative phosphorylation and glycolysis) suggesting their ascendant role with differentiation in T21 neurogenesis. Seven dysregulated clusters belong to receptor signaling pathways and these were evident at both stages of differentiation implying a critical role for dysfunctional intercellular communication and ECM in T21. Fold enrichment scores of annotated clusters are shown for NPC (green) and DiffNPC (grey). The complete clustering data are summarized in Supplemental Table S5