Spectacular advances in technology and computational biology spawned in large
part by the Human Genome Project have been instrumental in transforming the field of
embryonic stem cell biology. From the findings reported in the last decade it is clear that
properties unique to embryonic stem cells (ESCs) are regulated not by individual genes but
by complex gene networks that include both genes and ~22 nt noncoding microRNAs that
act to integrate multiple genes across diverse signaling pathways to regulate self-renewal
and differentiation. In this chapter we will discuss the evolution of our understanding of
regulatory networks underlying stem cell self-renewal and pluripotency made possible
through highthroughput genomic studies. In the last decade molecular technologies that
revealed key transcription and epigenetic factors in ESCs have given way to
highthroughput microarray and Next Generation Sequencing technologies. These largescale
genomics datasets analyzed through the latest bioinformatic and computational
methods have been instrumental in transforming the field of embryonic stem cells. We will
trace the history of ES cells to briefly discuss key genes and microRNAs that have been
established to regulate self-renewal and pluripotency in mouse and human prior to the
genomics revolution. We will then discuss the latest technologies and computational
algorithms that have been instrumental in revealing genome-wide changes associated with
self-renewal and differentiation at the genetic and epigenetic levels to yield the current
systems-level understanding of embryonic stem cells.
Keywords: miRNA, stem cells, pluripotency, epigenome, reprogramming,
microarrays, gene networks, Next generation sequencing (NGS), Chromatin
immunoprecipitation (ChIP), target prediction, iPSCs, bioinformatics, differentiation,
polycomb group proteins (PcGs), methylation, transcription factors.
