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Astroglia induce neurogenesis from adult neural stem cells

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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Figure 1: Differentiation of adult neural stem cells in a defined medium without serum.
Figure 2: Distinct effects of primary astrocytes and neurons on the fate choice of adult neural stem cells.
Figure 3: Effects of astrocytes on the survival, proliferation and neuronal fate commitment of adult neural stem cells.
Figure 4: Astrocytes increase the rates of proliferation and neuronal fate commitment of adult neural stem cells.
Figure 5: Intimate association of proliferating cells with GFAP+ astrocytes in the dentate gyrus of adult hippocampus.
Figure 6: Mature astrocytes from adult hippocampus, but not adult spinal cord, promote neurogenesis from adult stem cells.

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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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Correspondence to Charles F. Stevens or Fred H. Gage.

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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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