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

Ahmi Ben-Yehudah,Calvin Simerly,Carlos Castro,Brian P Hermann,Charles A Easley,Kyle E Orwig,Shoukhrat Mitalipov,Gerald Schatten

doi:10.1186/scrt24

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.

Highlights

To identify the mechanisms underlying pluripotency, a number of studies have been carried out, and these have been recently summarized [1]
Differentiation of expression features with other pluripotent cells (ESCs) recapitulates the earliest stages of human development, and understanding the gene regulatory networks in these cells will enhance our knowledge of the regulation of the earliest stages of development
Several groups have shown the ability of mouse, nonhuman primate and human ESCs to differentiate into germ cell lineages, in vitro-derived primordial germ cells (PGCs) [63-79]

Summary

Introduction

To identify the mechanisms underlying pluripotency, a number of studies have been carried out, and these have been recently summarized [1]. After 2 weeks of culture, these mouse iPS cells exhibited similar characteristics to ESCs, such as alkaline phosphatase activity, expression of SSEA-1 and Nanog (two pluripotency markers), and the ability to differentiate into all three germ layers (endoderm, ectoderm and mesoderm) via in vitro differentiation or teratoma formation in immunodeficient mice.

Results

Conclusion