Elsevier

Neuroscience

Volume 164, Issue 3, 15 December 2009, Pages 1044-1056
Neuroscience

Cellular Neuroscience
Research Paper
Cellular organization of the central canal ependymal zone, a niche of latent neural stem cells in the adult mammalian spinal cord

https://doi.org/10.1016/j.neuroscience.2009.09.006Get rights and content

Abstract

A stem cell's microenvironment, or “niche,” is a critical regulator of its behaviour. In the adult mammalian spinal cord, central canal ependymal cells possess latent neural stem cell properties, but the ependymal cell niche has not yet been described. Here, we identify important similarities and differences between the central canal ependymal zone and the forebrain subventricular zone (SVZ), a well-characterized niche of neural stem cells. First, direct immunohistochemical comparison of the spinal cord ependymal zone and the forebrain SVZ revealed distinct patterns of neural precursor marker expression. In particular, ependymal cells in the spinal cord were found to be bordered by a previously uncharacterized sub-ependymal layer, which is relatively less elaborate than that of the SVZ and comprised of small numbers of astrocytes, oligodendrocyte progenitors and neurons. Cell proliferation surrounding the central canal occurs in close association with blood vessels, but unlike in the SVZ, involves mainly ependymal rather than sub-ependymal cells. These proliferating ependymal cells typically self-renew rather than produce transit-amplifying progenitors, as they generate doublets of progeny that remain within the ependymal layer and show no evidence of a lineage relationship to sub-ependymal cells. Interestingly, the dorsal pole of the central canal was found to possess a sub-population of tanycyte-like cells that express markers of both ependymal cells and neural precursors, and their presence correlates with higher numbers of dorsally proliferating ependymal cells. Together, these data identify key features of the spinal cord ependymal cell niche, and suggest that dorsal ependymal cells possess the potential for stem cell activity. This work provides a foundation for future studies aimed at understanding ependymal cell regulation under normal and pathological conditions.

Section snippets

Animals

Experiments were conducted in accordance with the guidelines of the Canadian Council of Animal Care and were approved by the institutional Animal Care committee. A total of 70 two-month-old CD1 mice (Charles River Laboratories, St. Constant, QC, Canada) were used. For bromodeoxyuridine (BrdU) incorporation experiments, mice were administered three 100 μl intraperitoneal injections of BrdU (Sigma, 1.5 mg/injection) at 3 hour intervals, and were sacrificed either 1 or 21 days later.

Neurosphere cultures from the adult spinal cord

Mice were

Isolation and characterization of neurospheres from the adult mouse lumbar spinal cord

Multipotent neurospheres can be cultured from the adult mouse spinal cord (Weiss et al., 1996, Meletis et al., 2008). We were able to generate neurosphere cultures from the adult mouse lumbar spinal cord (Fig. 1) that expanded rapidly in vitro (Fig. 1a–d) and expressed typical neural stem cell markers such as Nestin, Sox2 and CD133 (Fig. 1e–j). Although neurogenesis does not occur in the adult spinal cord, spinal cord-derived neurospheres differentiated into neurons, astrocytes and

Discussion

Unlike the highly neurogenic astrocyte-like stem cells of the forebrain SVZ, ependymal cells of the spinal cord are normally relatively quiescent, only displaying stem cell properties following tissue injury or in culture (Frisen et al., 1995, Johansson et al., 1999, Martens et al., 2002, Meletis et al., 2008). In the present study, we analyzed the cellular organization of the spinal cord ependymal cell niche. We show that the spinal cord ependymal zone possesses many key features of the SVZ

Conclusion

Spinal cord ependymal cells have neural stem cell potential both in vitro and following tissue injury in vivo. Here, we found that they do not display multilineage potential or the ability to produce transit amplifying progenitors under normal conditions. Analysis of the ependymal cell niche revealed a previously unrecognized level of cellular heterogeneity and complexity, and indicated that many of the key elements of the forebrain stem cell niche are in fact present. However, these elements

Acknowledgments

This work was supported by funds from the Canadian Foundation for Innovation and the Université de Montréal. KF is a Canada Research Chair in Stem Cell Neurobiology. The authors are grateful to Meriem Bouab for helpful comments, to Dr. Fanie Barnabé-Heider for critical reading of the manuscript, and to Dr. Mustapha Riad and Dr. Laurent Descarries for technical advice.

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