Systems biology discoveries using non-human primate pluripotent stem and germ cells: novel gene and genomic imprinting interactions as well as unique expression patterns

Abstract

The study of pluripotent stem cells has generated much interest in both biology and medicine. Understanding the fundamentals of biological decisions, including what permits a cell to maintain pluripotency, that is, its ability to self-renew and thereby remain immortal, or to differentiate into multiple types of cells, is of profound importance. For clinical applications, pluripotent cells, including both embryonic stem cells and adult stem cells, have been proposed for cell replacement therapy for a number of human diseases and disorders, including Alzheimer's, Parkinson's, spinal cord injury and diabetes. One challenge in their usage for such therapies is understanding the mechanisms that allow the maintenance of pluripotency and controlling the specific differentiation into required functional target cells. Because of regulatory restrictions and biological feasibilities, there are many crucial investigations that are just impossible to perform using pluripotent stem cells (PSCs) from humans (for example, direct comparisons among panels of inbred embryonic stem cells from prime embryos obtained from pedigreed and fertile donors; genomic analysis of parent versus progeny PSCs and their identical differentiated tissues; intraspecific chimera analyses for pluripotency testing; and so on). However, PSCs from nonhuman primates are being investigated to bridge these knowledge gaps between discoveries in mice and vital information necessary for appropriate clinical evaluations. In this review, we consider the mRNAs and novel genes with unique expression and imprinting patterns that were discovered using systems biology approaches with primate pluripotent stem and germ cells.

Figure 1

Ingenuity analysis identifies novel gene networks involved in the maintenance of pluripotency. Genes over-expressed in non-human primate embryonic stem cells compared to fibroblasts are depicted in red. Genes shaded in green are over-expressed in fibroblasts. Genes that were differentially expressed in both of two previous studies [1,117] could be identified in this representative pathway. For this analysis we compared all genes with a known Entrez gene ID.

Figure 2

Non-coding RNAs can be identified as members of pluripotent pathways using Ingenuity. Ingenuity analysis shows that genes known to be involved in stemness (Nanog and Sox-2) are over-expressed (red) in non-human primate embryonic stem cells (nhpESCs) compared to fibroblasts. In addition, we could identify non-coding RNAs that were over-expressed in nhpESCs and associated with Nanog. For this analysis we compared all genes with a known Entrez gene ID.