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Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.

Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V - J. Cell Biol. (2003)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.

ABSTRACT
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.

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Developmental regulation of neural markers in CNP-GFP lineage cells. This scheme represents a summary of the antigenic markers expressed at different stages of neuronal differentiation of NG2+/CNP-GFP+ cells in the postnatal hippocampus.
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fig10: Developmental regulation of neural markers in CNP-GFP lineage cells. This scheme represents a summary of the antigenic markers expressed at different stages of neuronal differentiation of NG2+/CNP-GFP+ cells in the postnatal hippocampus.

Mentions: In the adult brain, we observed that early post-mitotic CNP-GFP+ immature hippocampal neurons expressing TOAD-64 (Cameron and McKay, 2001) were also NG2+ and displayed high levels of GFP, whereas more differentiated NeuN+/CNP-GFP+ neurons were NG2− and all exhibited low levels of GFP fluorescence. This finding indicates that NG2 proteoglycan expression and CNP gene promoter activity, as assessed by GFP fluorescence intensity, are inversely correlated with the progression of neuronal differentiation in vivo. These results are consistent with our in vitro data showing that the lineage continuum between NG2+ cells and their neuronal and astroglial progeny encompassed intermediate stages of commitment, which displayed low levels of GFP expression and the differentiated neural cell markers GFAP or NeuN. Hence, altogether these results delineate a possible developmental link between a defined class of adult progenitor cells expressing NG2 chondroitin proteoglycan and the CNP gene, and newborn postnatal hippocampal neurons (Fig. 10) . Although we cannot assess with the present model to what extent NG2+/CNP-GFP+ postnatal progenitor cells may totally repress CNP gene transcription during terminal stages of neuronal differentiation in vivo, we propose the following developmental scheme of postnatal/adult neurogenesis from NG2+/CNP-GFP+ cells in the hippocampus: NG2+/CNP-GFP+++ → TOAD-64+/NG2+/CNP-GFP2+ → NeuN+/NG2−/CNP-GFP+ → NeuN+/NG2−/CNP-GFP− (Fig. 10).


Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.

Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V - J. Cell Biol. (2003)

Developmental regulation of neural markers in CNP-GFP lineage cells. This scheme represents a summary of the antigenic markers expressed at different stages of neuronal differentiation of NG2+/CNP-GFP+ cells in the postnatal hippocampus.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172886&req=5

fig10: Developmental regulation of neural markers in CNP-GFP lineage cells. This scheme represents a summary of the antigenic markers expressed at different stages of neuronal differentiation of NG2+/CNP-GFP+ cells in the postnatal hippocampus.
Mentions: In the adult brain, we observed that early post-mitotic CNP-GFP+ immature hippocampal neurons expressing TOAD-64 (Cameron and McKay, 2001) were also NG2+ and displayed high levels of GFP, whereas more differentiated NeuN+/CNP-GFP+ neurons were NG2− and all exhibited low levels of GFP fluorescence. This finding indicates that NG2 proteoglycan expression and CNP gene promoter activity, as assessed by GFP fluorescence intensity, are inversely correlated with the progression of neuronal differentiation in vivo. These results are consistent with our in vitro data showing that the lineage continuum between NG2+ cells and their neuronal and astroglial progeny encompassed intermediate stages of commitment, which displayed low levels of GFP expression and the differentiated neural cell markers GFAP or NeuN. Hence, altogether these results delineate a possible developmental link between a defined class of adult progenitor cells expressing NG2 chondroitin proteoglycan and the CNP gene, and newborn postnatal hippocampal neurons (Fig. 10) . Although we cannot assess with the present model to what extent NG2+/CNP-GFP+ postnatal progenitor cells may totally repress CNP gene transcription during terminal stages of neuronal differentiation in vivo, we propose the following developmental scheme of postnatal/adult neurogenesis from NG2+/CNP-GFP+ cells in the hippocampus: NG2+/CNP-GFP+++ → TOAD-64+/NG2+/CNP-GFP2+ → NeuN+/NG2−/CNP-GFP+ → NeuN+/NG2−/CNP-GFP− (Fig. 10).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus