Abstract
BackgroundHuman embryonic stem (ES) cells hold great promise for medicine and science. The transcriptome of human ES cells has been studied in detail in recent years. However, no systematic analysis has yet addressed whether gene expression in human ES cells may be regulated in chromosomal domains, and no chromosomal domains of coexpression have been identified.ResultsWe report the first transcriptome coexpression map of the human ES cell and the earliest stage of ES differentiation, the embryoid body (EB), for the analysis of how transcriptional regulation interacts with genomic structure during ES self-renewal and differentiation. We determined the gene expression profiles from multiple ES and EB samples and identified chromosomal domains showing coexpression of adjacent genes on the genome. The coexpression domains were not random, with significant enrichment in chromosomes 8, 11, 16, 17, 19, and Y in the ES state, and 6, 11, 17, 19 and 20 in the EB state. The domains were significantly associated with Giemsa-negative bands in EB, yet showed little correlation with known cytogenetic structures in ES cells. Different patterns of coexpression were revealed by comparative transcriptome mapping between ES and EB.ConclusionThe findings and methods reported in this investigation advance our understanding of how genome organization affects gene expression in human ES cells and help to identify new mechanisms and pathways controlling ES self-renewal or differentiation.
Highlights
Human embryonic stem (ES) cells hold great promise for medicine and science
Transcriptome maps showing regional similarities illustrate the existence of chromosomal domains of gene coexpression and transcriptional regulation operating at the local
The transcriptome map provides information on transcriptional events operating at the local chromosome level in ES cells and localized coexpression of genes during differentiation
Summary
Human embryonic stem (ES) cells hold great promise for medicine and science. The transcriptome of human ES cells has been studied in detail in recent years. Transcriptome maps showing regional similarities illustrate the existence of chromosomal domains of gene coexpression and transcriptional regulation operating at the local (page number not for citation purposes). Transcriptome mapping analyses have been based on data generated from a variety of experimental techniques, including Expressed Sequence Tags [9], Serial Analysis of Gene Expression [8], and microarray [7]. All of these studies have revealed interesting and novel patterns of transcriptome in relation to genomic organization, molecular evolution, and biological functions
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