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Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration

Abstract

The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day1. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain2,3,4,5,6,7, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown. Here we describe a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. This astrocytic ribbon has not been observed in other vertebrates studied. Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as neural stem cells in a niche of unique organization in the adult human brain.

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Figure 1: Dense ribbon of SVZ astrocytes in the adult human brain.
Figure 2: Characteristics of adult human SVZ astrocytes.
Figure 3: Human SVZ astrocytes as neural progenitors.
Figure 4: The human SVZ–olfactory trigone connection: no evidence for neuronal chain migration to the olfactory bulbs.

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Acknowledgements

We thank G. E. Vates and J. W. Chiong for comments on the manuscript; A. Bollen, D. Gaskin, T. Tihan and S. R. VandenBerg for assistance with pathology material; A. Leong for stealth neuronavigational imagery; and Z. Mirzadeh for imaging. This work was supported by a gift from Frances and John Bowes, by the William Siebrandt Glioblastoma Fund and grants from the NIH. A.A-B. is the Heather and Melanie Muss Professor. N.S. is supported by the HHMI and an American Brain Tumor Association David B. Anderson Fellowship. A.D.T. is supported by the Damon Runyon Cancer Research Foundation.

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Correspondence to Nader Sanai or Arturo Alvarez-Buylla.

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Supplementary information

Supplementary Methods

Additional methodological information regarding the quantification of cell proliferation and calculation of astrocyte growth curves. (DOC 19 kb)

Supplementary Figures (JPG 142 kb)

Supplementary Figure Legends (DOC 19 kb)

Supplementary Table 1

List of collected intraoperative human specimens. (PDF 23 kb)

Supplementary Table 2

List of collected autopsied human specimens. (PDF 21 kb)

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Sanai, N., Tramontin, A., Quiñones-Hinojosa, A. et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427, 740–744 (2004). https://doi.org/10.1038/nature02301

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