Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System

New neurons are continuously added in specific regions of the adult mammalian central nervous system. These neurons are derived from multipotent stem cells whose identity has been enigmatic. In this work, we present evidence that ependymal cells are neural stem cells. Ependymal cells give rise to a rapidly proliferating cell type that generates neurons that migrate to the olfactory bulb. In response to spinal cord injury, ependymal cell proliferation increases dramatically to generate migratory cells that differentiate to astrocytes and participate in scar formation. These data demonstrate that ependymal cells are neural stem cells and identify a novel process in the response to central nervous system injury.

[1]  L. Philipson,et al.  HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Kenji Matsuno,et al.  Notch signaling. , 1995, Science.

[3]  S. Mcconnell,et al.  Cleavage orientation and the asymmetric inheritance of notchl immunoreactivity in mammalian neurogenesis , 1995, Cell.

[4]  S. Artavanis-Tsakonas,et al.  Alterations in Notch signaling in neoplastic lesions of the human cervix. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  U. Lendahl,et al.  Expression of Notch 1, 2 and 3 is regulated by epithelial-mesenchymal interactions and retinoic acid in the developing mouse tooth and associated with determination of ameloblast cell fate , 1995, The Journal of cell biology.

[6]  U. Lendahl,et al.  Expression of the class VI intermediate filament nestin in human central nervous system tumors. , 1992, Cancer research.

[7]  S. Wiegand,et al.  Injury‐induced Regulation of Ciliary Neurotrophic Factor mRNA in the Adult Rat Brain , 1993, The European journal of neuroscience.

[8]  Brent A. Reynolds,et al.  Multipotent CNS Stem Cells Are Present in the Adult Mammalian Spinal Cord and Ventricular Neuroaxis , 1996, The Journal of Neuroscience.

[9]  J. Sanes.  Analysing cell lineage with a recombinant retrovirus , 1989, Trends in Neurosciences.

[10]  M. R. Bigio,et al.  The ependyma: A protective barrier between brain and cerebrospinal fluid , 1995 .

[11]  R. McKay,et al.  Single factors direct the differentiation of stem cells from the fetal and adult central nervous system. , 1996, Genes & development.

[12]  S. Weiss,et al.  Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. , 1992, Science.

[13]  G. Weinmaster,et al.  Notch2: a second mammalian Notch gene. , 1992, Development.

[14]  J. Altman,et al.  Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats , 1965, The Journal of comparative neurology.

[15]  Maria B. Luskin,et al.  Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone , 1993, Neuron.

[16]  J. García-Verdugo,et al.  Cellular Composition and Three-Dimensional Organization of the Subventricular Germinal Zone in the Adult Mammalian Brain , 1997, The Journal of Neuroscience.

[17]  B. Davidson,et al.  Recombinant Adenovirus: A Gene Transfer Vector for Study and Treatment of CNS Diseases , 1997, Experimental Neurology.

[18]  David J. Anderson,et al.  Regulatory Mechanisms in Stem Cell Biology , 1997, Cell.

[19]  Fred H. Gage,et al.  The Adult Rat Hippocampus Contains Primordial Neural Stem Cells , 1997, Molecular and Cellular Neuroscience.

[20]  C. Lois,et al.  Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  E. Parati,et al.  Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  Brent A. Reynolds,et al.  Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells , 1994, Neuron.

[23]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[24]  S. Weiss,et al.  Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. , 1996, Developmental biology.

[25]  M. Risling,et al.  Rapid, widespread, and longlasting induction of nestin contributes to the generation of glial scar tissue after CNS injury , 1995, The Journal of cell biology.

[26]  M. Luskin,et al.  Strategies utilized by migrating neurons of the postnatal vertebrate forebrain , 1998, Trends in Neurosciences.

[27]  Ihor R. Lemischka,et al.  Developmental potential and dynamic behavior of hematopoietic stem cells , 1986, Cell.

[28]  R. McKay,et al.  CNS stem cells express a new class of intermediate filament protein , 1990, Cell.

[29]  F. Gage,et al.  Stem cells of the central nervous system. , 1998, Current opinion in neurobiology.

[30]  S. Finklestein,et al.  Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds , 1988, Brain Research.

[31]  F. Gage,et al.  Isolation, characterization, and use of stem cells from the CNS. , 1995, Annual review of neuroscience.

[32]  S. Temple,et al.  A self-renewing multipotential stem cell in embryonic rat cerebral cortex , 1994, Nature.

[33]  C. Cepko,et al.  Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. I.,et al.  Neural Field Continuum Limits and the Structure–Function Partitioning of Cognitive–Emotional Brain Networks , 2023, Biology.