Research article

Transcriptome coexpression map of human embryonic stem cells

Huai Li^1†, Ying Liu^2†, Soojung Shin², Yu Sun¹, Jeanne F Loring³, Mark P Mattson², Mahendra S Rao^4,5* and Ming Zhan1^*

• * Corresponding authors: Mahendra S Rao raomah@mail.nih.gov - Ming Zhan1 zhanmi@mail.nih.gov

• † Equal contributors

Author Affiliations

¹ Bioinformatics Unit, Branch of Research Resources, National Institute on Aging, NIH, Baltimore, MD 21224, USA

² Laboratory of Neurosciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA

³ The Burnham Institute, La Jolla, CA92037, USA

⁴ Neurosciences Program, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA

⁵ The CRL, Invitrogen Corp, 1620 Faraday Ave, Carlsbad, CA 92008, USA

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BMC Genomics 2006, 7:103 doi:10.1186/1471-2164-7-103

Published: 2 May 2006

Abstract

Background

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. 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.

Results

We 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.

Conclusion

The 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.