Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo.
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.
Mukouyama
Yoh-suke
YS
Howard Hughes Medical Institute and Division of Biology 216-76, California Institute of Technology, 1201 East California Boulevard, Pasadena, CA 91125, USA.
Deneen
Benjamin
B
Lukaszewicz
Agnès
A
Novitch
Bennett G
BG
Wichterle
Hynek
H
Jessell
Thomas M
TM
Anderson
David J
DJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D002469:Cell Separation; D017690:Cell Transplantation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D002642:Chick Embryo; D004847:Epithelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016256:Lewis X Antigen / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors; D014183:Transplantation, Heterologous
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D016256:Lewis X Antigen; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C512773:Olig2 protein, mouse