Abstract
During an investigation of the mechanisms through which the local environment controls the fate specification of adult neural stem cells, we discovered that adult astrocytes from hippocampus are capable of regulating neurogenesis by instructing the stem cells to adopt a neuronal fate. This role in fate specification was unexpected because, during development, neurons are generated before most of the astrocytes. Our findings, together with recent reports that astrocytes regulate synapse formation and synaptic transmission, reinforce the emerging view that astrocytes have an active regulatory role—rather than merely supportive roles traditionally assigned to them—in the mature central nervous system.
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References
Temple, S. & Alvarez-Buylla, A. Stem cells in the adult mammalian central nervous system. Curr. Opin. Neurobiol. 9, 135–141 (1999)
Gage, F. H. Mammalian neural stem cells. Science 287, 1433–1438 (2000)
Temple, S. The development of neural stem cells. Nature 414, 112–117 (2001)
Rakic, P. Adult neurogenesis in mammals: an identity crisis. J. Neurosci. 22, 614–618 (2002)
Horner, P. et al. Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J. Neurosci. 20, 2218–2228 (2000)
Magavi, S. S., Leavitt, B. R. & Macklis, J. D. Induction of neurogenesis in the neocortex of adult mice. Nature 405, 892–893 (2000)
Kornack, D. R. & Rakic, P. Cell proliferation without neurogenesis in adult primate neocortex. Science 294, 2127–2130 (2001)
Reynolds, B. A. & Weiss, S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710 (1992)
Lois, C. & Alvarez-Buylla, A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc. Natl Acad. Sci. USA 90, 2074–2077 (1993)
Palmer, T. D., Takahashi, J. & Gage, F. H. The adult rat hippocampus contains primordial neural stem cells. Mol. Cell. Neurosci. 8, 389–404 (1997)
Shihabuddin, L. S., Ray, J. & Gage, F. H. FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord. Exp. Neurol. 148, 577–586 (1997)
Kehl, L. J., Fairbanks, C. A., Laughlin, T. M. & Wilcox, G. L. Neurogenesis in postnatal rat spinal cord: a study in primary culture. Science 276, 586–589 (1997)
Palmer, T. D., Markakis, E. A., Willhoite, A. R., Safar, F. & Gage, F. H. Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J. Neurosci. 19, 8487–8497 (1999)
Kondo, T. & Raff, M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 289, 1754–1757 (2000)
Suhonen, J. O., Peterson, D. A., Ray, J. & Gage, F. H. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 383, 624–627 (1996)
Shihabuddin, L. S., Horner, P. J., Ray, J. & Gage, F. H. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J. Neurosci. 20, 8727–8735 (2000)
Takahashi, J., Palmer, T. D. & Gage, F. H. Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures. J. Neurobiol. 38, 65–81 (1999)
Lendahl, U., Zimmerman, L. B. & McKay, R. D. CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595 (1990)
Qian, X. et al. Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28, 69–80 (2000)
Palmer, T. D., Willhoite, A. & Gage, F. H. Vascular niche for adult hippocampal neurogenesis. J. Comp. Neurol. 425, 479–494 (2000)
Barres, B. A. & Raff, M. C. Axonal control of oligodendrocyte development. J. Cell Biol. 147, 1123–1238 (1999)
Ridet, J. R., Malhotra, S. K., Privat, A. & Gage, F. H. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci. 20, 570–577 (1997)
Goslin, K., Asmussen, H. & Banker, G. in Culturing Nerve Cells (eds Banker, G. & Goslin, K.) 339–370 (The MIT Press, Cambridge, Massachusetts, 1998)
Lim, D. A. & Alvarez-Buylla, A. Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc. Natl Acad. Sci. USA 96, 7526–7536 (1999)
Banker, G. A. Trophic interactions between astroglial cells and hippocampal neurons in culture. Science 209, 809–810 (1980)
Cowan, W. M., Stanfield, B. B. & Kishi, K. in Current Topics in Developmental Biology (ed. Hunt, K.) 103–157 (Academic, New York, 1980)
Nicholls, J. G., Martin, A. R. & Wallace, B. G. From Neuron To Brain 3rd edn, 149–152 (Sinauer, Sunderland, Massachussetts, 1992)
Kandel, E. R., Schwartz, J. H. & Jessell, T. M. Principle of Neural Science (McGraw-Hill, New York, 2000)
Kuhn, H. G., Dickinson-Anson, H. & Gage, F. H. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027–2033 (1996)
Pixley, S. K. CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells. Neuron 8, 1191–1204 (1992)
Ullian, E. M., Sapperstein, S. K., Christopherson, K. S. & Barres, B. A. Control of synapse number by glia. Science 291, 657–661 (2001)
Mauch, D. H. et al. CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354–1357 (2001)
Haydon, P. G. GLIA: listening and talking to the synapse. Nature Rev. Neurosci. 2, 185–193 (2001)
Lino, M. K. et al. Glia-synapse interaction through Ca2 +-permeable AMPA receptors in Bergmann glia. Science 292, 926–929 (2001)
Oliet, S. H. et al. Control of glutamate clearance and synaptic efficacy by glial coverage of neurons. Science 292, 923–926 (2001)
Smit, A. B. et al. A glia-derived acetylcholine-binding protein that modulates synaptic transmission. Nature 411, 261–268 (2001)
Noctor, S. C., Flint, A. C., Weissman, T. A., Dammerman, R. S. & Kriegstein, A. R. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001)
Miyata, T., Kawaguchi, A., Okano, H. & Ogawa, M. Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31, 727–741 (2001)
Lim, D. A. et al. Noggin antagonizes BMP signalling to create a niche for adult neurogenesis. Neuron 28, 713–726 (2000)
Bekkers, J. M. & Stevens, C. F. Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture. Proc. Natl Acad. Sci. USA 88, 7834–7838 (1991)
Noble, M. & Mayer-Proschel, M. in Culturing Nerve Cells (eds Banker, G. & Golsin, K.) 499–544 (The MIT Press, Cambridge, Massachusetts, 1998)
Schwartz, J. P. & Wilson, D. J. Preparation and characterization of type 1 astrocytes cultured from adult rat cortex, cerebellum, and striatum. Glia 5, 75–80 (1992)
Acknowledgements
We thank M. L. Gage and J. Sullivan for comments. This work was supported in part by grants from the National Institutes of Health, Howard Hughes Medical Institute, Christopher Reeve Paralysis Foundation, the National Institute of Aging, the Michael J. Fox Foundation, Project ALS and The Lookout Fund. H.S. is an associate and C.F.S. is an investigator of the Howard Hughes Medical Institute.
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Song, H., Stevens, C. & Gage, F. Astroglia induce neurogenesis from adult neural stem cells. Nature 417, 39–44 (2002). https://doi.org/10.1038/417039a
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DOI: https://doi.org/10.1038/417039a
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