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Olig2^+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo

Mukouyama, Yoh-suke and Deneen, Benjamin and Lukaszewwicz, Agnès and Novitch, Bennett G. and Wichterle, Hynek and Jessell, Thomas M. and Anderson, David J. (2006) Olig2^+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo. Proceedings of the National Academy of Sciences of the United States of America, 103 (5). pp. 1551-1556. ISSN 0027-8424. PMCID PMC1345718. doi:10.1073/pnas.0510658103.

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Neurons and glia are thought to arise from multipotent and self-renewing stem cells, which comprise the majority of neuroepithelial cells in the ventricular zone (VZ) of the early embryonic CNS. However, this idea remains to be tested rigorously, because CNS stem cells have been identified only by using in vitro assays, from which their abundance in vivo cannot be directly inferred. In the hematopoietic system, stem cells are characterized by using prospective isolation and direct in vivo transplantation. Here we have used this approach to ask whether most VZ progenitors behave as stem cells in vivo. The best-studied region of the embryonic CNS for addressing this problem is, arguably, the ventral spinal cord, within which progenitors in the motoneuron progenitor (pMN) domain sequentially generate motoneurons (MNs) and oligodendrocyte precursors (OPs). Virtually all VZ cells in pMN express the transcription factor Olig2. If most of these cells are stem cells, then they should maintain neurogenic potential, even at later, gliogenic stages. To test this hypothesis, we have prospectively isolated Olig2+ cells from murine embryonic day (E)9.5 and E13.5 spinal cord and directly transplanted them to E2 chick spinal cord. Transplanted E9.5 cells generate both neurons, including MNs and OPs, whereas E13.5 cells generate. The observation that most Olig2+ progenitors do not maintain neurogenic potential into the period of gliogenesis argues that they do not self-renew. These results do not support the commonly held view that most neuroepithelial cells in the embryonic CNS VZ are stem cells in vivo.

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Anderson, David J.0000-0001-6175-3872
Additional Information:© 2006 by the National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by Thomas M. Jessell, December 9, 2005. Published online before print January 23, 2006, 10.1073/pnas.0510658103 We thank R. Diamond and S. L. Adams for FACS assistance; S. Pease, B. Kennedy, and the staff of the Transgenic Animal Facility at California Institute of Technology (Caltech) for assistance with mouse breeding and care; the Biological Imaging Center at Caltech for imaging assistance; I. Weissman (Stanford University) for antibody CD133; G. Mosconi for laboratory management; J.-S. Chang and M. Martinez for technical support; G. Mancuso for administrative assistance; C. Hochstim, L. Gabay, S. Lowell, M. Yui, and P. Lwigle for helpful discussion; and Anderson lab members for technical help and discussion. This work was supported by funding from the Howard Hughes Medical Institute and the National Institiutes of Health. T.M.J. and D.J.A. are Investigators of the Howard Hughes Medical Institute. Author contributions: Y.-s.M. and D.J.A. designed research; Y.-s.M., B.D., and A.L. performed research; B.G.N., H.W., and T.M.J. contributed new reagents/analytic tools; Y.-s.M., B.D., and A.L. analyzed data; and Y.-s.M., T.M.J., and D.J.A. wrote the paper. Conflict of interest statement: No conflicts declared.
Subject Keywords:CNS stem cells; neuroepithelial cells; in vivo transplantation
Issue or Number:5
PubMed Central ID:PMC1345718
Record Number:CaltechAUTHORS:MUKpnas06
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Official Citation:Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo Yoh-suke Mukouyama, Benjamin Deneen, Agnès Lukaszewicz, Bennett G. Novitch, Hynek Wichterle, Thomas M. Jessell, David J. Anderson Proceedings of the National Academy of Sciences Jan 2006, 103 (5) 1551-1556; DOI: 10.1073/pnas.0510658103
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1784
Deposited By: Archive Administrator
Deposited On:18 Feb 2006
Last Modified:08 Nov 2021 19:42

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