Identification of differential expressed genes between P-RPCs, ESC-RPCs and Dkk1 treated ESC-RPCs through genome-wide transcript profiling

Tumor formation constitutes a major obstacle to the clinical application of embryonic stem cells (ESCs). As P-RPCs could successfully integrate into host eyes without development of teratomas or NOG, we sought to identify differentially expressed genes between P-RPCs and ESC-RPCs through genome-wide transcript profiling. Inhibition of Wnt signaling by DKK1 promotes the commitment of ESC-RPCs to more mature retinal cells and reduces the occurrence of NOG to 3%. DKK1-treated ESC-RPCs efficiently integrate to the host retina, form synaptic connections and restore visual function. Here, we report that further differentiation of ESC-derived neural progenitors into retinal progenitor cells (ESC-RPCs) completely eliminates teratomas in ocular transplantation. However, tumor-like neural overgrowth (NOG) occurs in 61% of transplanted eyes. ESC-RPCs were divided into two groups according to the differentiation stages for RNA extraction and hybridization on Affymetrix microarrays. Normal control ESC-RPCs (N) were represented the homogeneous populations of early stage expression profiles of immature ESC-RPCs. DKK1 treated ESC-RPCs (D) were represented the homogeneous populations of late stage expression profiles of further differetiated mature ESC-RPCs. To sought the pathways involved in the proliferation and oncogenesis of ESC-RPCs, the newborn C57 mice reitinal progenitor cells (R) were applied as negative control. Each group above had three independent biological repeats.