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.

NFE2L3 (NRF3): the Cinderella of the Cap‘n’Collar transcription factors

“…For instance, NFE2L3 was proposed to be used as a stemness marker gene since its mRNA levels had the highest fold change ([300-fold change) when comparing rhesus macaque fibroblasts to pluripotent stem cells [111,112]. This interesting result was confirmed by other laboratories using rhesus monkey embryonic stem cells transduced with specific transcription factors [113,114].…”

Ex Vivo Reconstitution of Arterial Endothelium by Embryonic Stem Cell-Derived Endothelial Progenitor Cells in Baboons

“…However, large animal models have demonstrated a better suitability for translation to humans, since a substantial body of evidence has clearly demonstrated differences between human and mouse ESCs [37][38][39]. A large Old World nonhuman primate, the baboon, has an advantage over other large models because of the high level of similarity of its physiological characteristics to those of humans [13,[40][41][42]. The results of the present study suggest that baboon ESCs represent a new research tool that is highly relevant for stem cell therapy in human, thus contributing to developing clinical application of stem cell therapies.…”

“…With regard to cell-based therapy, stem cell turnover is remarkably higher in small animals than in large ones [14]. That could cause fundamental differences in the stemness profile of therapeutic agents and in the signaling pathways that regulate the fate of ESCs [13]. In addition, the modes of stem cell delivery (dosage, time points, methods) have a profound effect on the efficacy of treatment.…”

“…After more than a decade of research with human and mouse ESCs, there is an increasing recognition of the need for nonhuman primate models for stem cell research and applications [9][10][11][12][13]. With regard to cell-based therapy, stem cell turnover is remarkably higher in small animals than in large ones [14].…”

Systems and Network Pharmacology Approaches to Cancer Stem Cells Research and Therapy

“…In this direction, Ben-Yehudah and colleagues using Ingenuity software identified system networks responsible for the regulation of the pluripotent state in nhpESCs and were able to create many gene networks (Figure 2B) [18]. The authors showed that most of these networks contained anticipated stem cell marker genes such as SOX2 , OCT-4 and NANOG .…”