QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/jcs.00049

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Billon, N. Articles by Raff, M. Search for Related Content PubMed PubMed Citation Articles by Billon, N. Articles by Raff, M. Social Bookmarking                         What's this?

Normal timing of oligodendrocyte development from genetically engineered, lineage-selectable mouse ES cells

¹ MRC Laboratory for Molecular Cell Biology and Cell Biology Unit and the Biology Department, University College London, London WC1E 6BT, UK
² Centre for Genome Research, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JQ, UK

^* Author for correspondence (e-mail: n.billon{at}ucl.ac.uk)

Accepted 7 July 2002

Oligodendrocytes are post-mitotic cells that myelinate axons in the vertebrate central nervous system (CNS). They develop from proliferating oligodendrocyte precursor cells (OPCs), which arise in germinal zones, migrate throughout the developing white matter and divide a limited number of times before they terminally differentiate. Thus far, it has been possible to purify OPCs only from the rat optic nerve, but the purified cells cannot be obtained in large enough numbers for conventional biochemical analyses. Moreover, the CNS stem cells that give rise to OPCs have not been purified, limiting one's ability to study the earliest stages of commitment to the oligodendrocyte lineage. Pluripotent, mouse embryonic stem (ES) cells can be propagated indefinitely in culture and induced to differentiate into various cell types. We have genetically engineered ES cells both to positively select neuroepithelial stem cells and to eliminate undifferentiated ES cells. We have then used combinations of known signal molecules to promote the development of OPCs from selected, ES-cell-derived, neuroepithelial cells. We show that the earliest stages of oligodendrocyte development follow an ordered sequence that is remarkably similar to that observed in vivo, suggesting that the ES-cell-derived neuroepithelial cells follow a normal developmental pathway to produce oligodendrocytes. These engineered ES cells thus provide a powerful system to study both the mechanisms that direct CNS stem cells down the oligodendrocyte pathway and those that influence subsequent oligodendrocyte differentiation. This strategy may also be useful for producing human cells for therapy and drug screening.

Key words: Oligodendrocyte, Development, ES cells, Genetic selection

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Oligodendrocyte differentiation from ES cells

JCS 2002 115: 1804. [Full Text]  

This article has been cited by other articles:

				B.-Y. Hu, Z.-W. Du, X.-J. Li, M. Ayala, and S.-C. Zhang Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects Development, May 1, 2009; 136(9): 1443 - 1452. [Abstract] [Full Text] [PDF]

				S. Briers, C. Crawford, W. A. Bickmore, and H. G. Sutherland KRAB zinc-finger proteins localise to novel KAP1-containing foci that are adjacent to PML nuclear bodies J. Cell Sci., April 1, 2009; 122(7): 937 - 946. [Abstract] [Full Text] [PDF]

				H. F. Jorgensen, A. Terry, C. Beretta, C. F. Pereira, M. Leleu, Z.-F. Chen, C. Kelly, M. Merkenschlager, and A. G. Fisher REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells Development, March 1, 2009; 136(5): 715 - 721. [Abstract] [Full Text] [PDF]

				C. Morey, N. R. Da Silva, P. Perry, and W. A. Bickmore Nuclear reorganisation and chromatin decondensation are conserved, but distinct, mechanisms linked to Hox gene activation Development, March 1, 2007; 134(5): 909 - 919. [Abstract] [Full Text] [PDF]

				L. S. Campos, L. Decker, V. Taylor, and W. Skarnes Notch, Epidermal Growth Factor Receptor, and beta1-Integrin Pathways Are Coordinated in Neural Stem Cells J. Biol. Chem., February 24, 2006; 281(8): 5300 - 5309. [Abstract] [Full Text] [PDF]

				R. R. E. Williams, V. Azuara, P. Perry, S. Sauer, M. Dvorkina, H. Jorgensen, J. Roix, P. McQueen, T. Misteli, M. Merkenschlager, et al. Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus J. Cell Sci., January 1, 2006; 119(1): 132 - 140. [Abstract] [Full Text] [PDF]

				G. Keller Embryonic stem cell differentiation: emergence of a new era in biology and medicine Genes & Dev., May 15, 2005; 19(10): 1129 - 1155. [Abstract] [Full Text] [PDF]

				J. C. Davila, G. G. Cezar, M. Thiede, S. Strom, T. Miki, and J. Trosko Use and Application of Stem Cells in Toxicology Toxicol. Sci., June 1, 2004; 79(2): 214 - 223. [Abstract] [Full Text] [PDF]

				S. Chambeyron and W. A. Bickmore Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription Genes & Dev., May 15, 2004; 18(10): 1119 - 1130. [Abstract] [Full Text] [PDF]

				K. G. Sylvester and M. T. Longaker Stem Cells: Review and Update Arch Surg, January 1, 2004; 139(1): 93 - 99. [Abstract] [Full Text] [PDF]