Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

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.


  1. Alvarez-Buylla, A., Garcia-Verdugo, J. M. & Tramontin, A. D. A unified hypothesis on the lineage of neural stem cells. Nature Rev. Neurosci. 2, 287–293 (2001)

    Article  CAS  Google Scholar 

  2. Pincus, D. W. et al. In vitro neurogenesis by adult human epileptic temporal neocortex. Clin. Neurosurg. 44, 17–25 (1997)

    CAS  PubMed  Google Scholar 

  3. Roy, N. S. et al. Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone. J. Neurosci. Res. 59, 321–331 (2000)

    Article  CAS  Google Scholar 

  4. Johansson, C. B., Svensson, M., Wallstedt, L., Janson, A. M. & Frisen, J. Neural stem cells in the adult human brain. Exp. Cell Res. 253, 733–736 (1999)

    Article  CAS  Google Scholar 

  5. Pagano, S. F. et al. Isolation and characterization of neural stem cells from the adult human olfactory bulb. Stem Cells 18, 295–300 (2000)

    Article  CAS  Google Scholar 

  6. Nunes, M. C. et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nature Med. 9, 439–447 (2003)

    Article  CAS  Google Scholar 

  7. Kukekov, V. G. et al. Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain. Exp. Neurol. 156, 333–344 (1999)

    Article  CAS  Google Scholar 

  8. Kornack, D. R. & Rakic, P. The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proc. Natl Acad. Sci. USA 98, 4752–4757 (2001)

    Article  ADS  CAS  Google Scholar 

  9. Alvarez-Buylla, A. & Garcia-Verdugo, J. M. Neurogenesis in adult subventricular zone. J. Neurosci. 22, 629–634 (2002)

    Article  CAS  Google Scholar 

  10. Pencea, V., Bingaman, K. D., Freedman, L. J. & Luskin, M. B. Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain. Exp. Neurol. 172, 1–16 (2001)

    Article  CAS  Google Scholar 

  11. Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–716 (1999)

    Article  CAS  Google Scholar 

  12. Laywell, E. D., Rakic, P., Kukekov, V. G., Holland, E. C. & Steindler, D. A. Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc. Natl Acad. Sci. USA 97, 13883–13888 (2000)

    Article  ADS  CAS  Google Scholar 

  13. Skogh, C. et al. Generation of regionally specified neurons in expanded glial cultures derived from the mouse and human lateral ganglionic eminence. Mol. Cell. Neurosci. 17, 811–820 (2001)

    Article  CAS  Google Scholar 

  14. Imura, T., Kornblum, H. I. & Sofroniew, M. V. The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP. J. Neurosci. 23, 2824–2832 (2003)

    Article  CAS  Google Scholar 

  15. 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)

    Article  ADS  CAS  Google Scholar 

  16. Chiasson, B. J., Tropepe, V., Morshead, C. M. & van der Kooy, D. Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J. Neurosci. 19, 4462–4471 (1999)

    Article  CAS  Google Scholar 

  17. Gritti, A. et al. Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents. J. Neurosci. 22, 437–445 (2002)

    Article  CAS  Google Scholar 

  18. Kirschenbaum, B. et al. In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain. Cereb. Cortex 4, 576–589 (1994)

    Article  CAS  Google Scholar 

  19. Palmer, T. D. et al. Cell culture. Progenitor cells from human brain after death. Nature 411, 42–43 (2001)

    Article  ADS  CAS  Google Scholar 

  20. Doetsch, F., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17, 5046–5061 (1997)

    Article  CAS  Google Scholar 

  21. Blakemore, W. F. & Jolly, R. D. The subependymal plate and associated ependyma in the dog. An ultrastructural study. J. Neurocytol. 1, 69–84 (1972)

    Article  CAS  Google Scholar 

  22. Perez-Martin, M. et al. Ependymal explants from the lateral ventricle of the adult bovine brain: a model system for morphological and functional studies of the ependyma. Cell Tissue Res. 300, 11–19 (2000)

    Article  CAS  Google Scholar 

  23. Eriksson, P. S. et al. Neurogenesis in the adult human hippocampus. Nature Med. 4, 1313–1317 (1998)

    Article  CAS  Google Scholar 

  24. Lim, D. A. & Alvarez-Buylla, A. Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc. Natl Acad. Sci. USA 96, 7526–7531 (1999)

    Article  ADS  CAS  Google Scholar 

  25. Song, H., Stevens, C. F. & Gage, F. H. Astroglia induce neurogenesis from adult neural stem cells. Nature 417, 39–44 (2002)

    Article  ADS  CAS  Google Scholar 

  26. Lois, C., Garcia-Verdugo, J. M. & Alvarez-Buylla, A. Chain migration of neuronal precursors. Science 271, 978–981 (1996)

    Article  ADS  CAS  Google Scholar 

  27. Bonfanti, L., Peretto, P., Merighi, A. & Fasolo, A. Newly-generated cells from the rostral migratory stream in the accessory olfactory bulb of the adult rat. Neuroscience 81, 489–502 (1997)

    Article  CAS  Google Scholar 

  28. Leel-Ossy, L. & Gati, I. Corpus amylaceum (polyglucosan body) in the peripheral olfactory system. Pathol. Oncol. Res. 4, 212–216 (1998)

    Article  CAS  Google Scholar 

  29. Smith, K. R., Frank, K. J. & Bucholz, R. D. The NeuroStation—a highly accurate, minimally invasive solution to frameless stereotactic neurosurgery. Comput. Med. Imaging Graph. 18, 247–256 (1994)

    Article  CAS  Google Scholar 

  30. McCarthy, K. D. & de Vellis, J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85, 890–902 (1980)

    Article  CAS  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Nader Sanai or Arturo Alvarez-Buylla.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing