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First published online February 1, 2007
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2006-0660v1
25/5/1298    most recent
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Submitted on October 27, 2006
Accepted on January 19, 2007

Tissue-Specific Stem Cells

Whole genome analysis of human neural stem cells derived from embryonic stem cells and stem and progenitor cells isolated from fetal tissue

Soojung Shin 1, Yu Sun 2, Ying Liu 1, Hanita Khaner 3, Smita Svant 4, Jingli Cai 5, Xiu Qin Xu 6, Bruce P. Davidson 6, Steven L. Stice 7, Alan K. Smith 4, Steven A. Goldman 8, Benjamin E. Reubinoff 3, Ming Zhan 2, Mahendra S. Rao 1, Jonathan D. Chesnut 1*

1 Stem cells and regenerative medicine, Invitrogen, Carlsbad, California
2 Bioinformatics Unit, Branch of Research Resources, NIA, NIH, Baltimore, Maryland
3 The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy & The Department of Gynecology, Hadassah University Hospital, Jerusalem, Israel
4 Theradigm Inc., Baltimore, Maryland
5 Thomas Jefferson University, Philadelphia, Pennsylvania
6 ES Cell International Pte Ltd, Helios, Singapore
7 University of Georgia, Athens, Georgia
8 University of Rochester, Rochester, New York

* To whom correspondence should be addressed. E-mail: Jon.Chesnut{at}invitrogen.com.


   Abstract

Multipotent neural stem cells (NSCs) have been derived from human embryonic stem cells (hESCs) as well as isolated from fetal tissues. However, there have been few exclusive markers of NSCs identified to date and the differences between NSCs from various sources are poorly understood. While cells isolated from these two sources share many important characteristics, it is not clear how closely they are related in terms of gene expression. Here we compare the gene expression profiles of 11 lines of NSCs derived from hESCs (ES_NSCs), 4 lines of NSCs isolated from fetus (F_NSCs), and 2 lines of restricted progenitors in order to characterize these cell populations and identify differences between NSCs derived from these two sources. We showed that ES_NSC were clustered together with high transcriptional similarities but distinguished from F_NSCs, Oligodendrocyte precursor cells (OPCs), and Astrocyte precursor cells (APCs). There were 17 genes expressed in both ES_NSC and F_NSC whose expression was not identified in restricted neural progenitors. Furthermore, the major differences between ES_NSC and F_NSC were mostly observed in genes related to the key neural differentiation pathways. Here we show that comparison of global gene expression profiles of ES_NSCs, F_NSCs and restricted neural progenitor cells makes it possible to identify some of the common characteristics of NSCs and differences between similar stem cell populations derived from hESC or isolated from fetal tissue.

Key Words. Large scale genomic analysis, neural stem cells, human embryonic stem cells, adult stem cells, differentiation, lineage restricted precursor cells




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