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¹ Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010
² Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
³ Gene Transfer Laboratory, Hematopoiesis Section, Flow Cytometry Core Unit, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892

Address correspondence to Dr. Vittorio Gallo, Center for Neuroscience Research, Children's Research Institute, Room 5345, Children's National Medical Center, 111 Michigan Ave., N.W., Washington, DC 20010-2970. Tel.: (202) 884-4996. Fax: (202) 884-4988. E-mail: vgallo{at}cnmcresearch.org

Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan–positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2⁺ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2⁺ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.

Key Words: stem cell; oligodendrocyte progenitor; differentiation; adult neurogenesis; glia

The online version of this article includes supplemental material.

S. Belachew's present address is Center for Cellular and Molecular Neurobiology, Department of Neurology, University of Liège, B-4000 Liège, Belgium.

^* Abbreviations used in this paper: CNP, 2',3'-cyclic nucleotide 3'-phosphodiesterase; CNS, central nervous system; DNQX, 6,7-dinitro-2,3-quinoxalinedione; GABA, -aminobutyric acid; GAD, glutamate decarboxylase; GFAP, glial fibrillary acidic protein; MAP, microtubule-associated protein; NeuN, neuronal nuclei protein; NSC, neural stem cell; OPC, oligodendrocyte progenitor cell; PCNA, proliferating cell nuclear antigen; PLP, proteolipid protein; SCM, stem cell medium; SVZ, subventricular zone; TOAD-64, turned on after division, 64 kD; TTX, tetrodotoxin.

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