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Life Sci Alliance ; 3(7)2020 07.
Article in English | MEDLINE | ID: mdl-32482782

ABSTRACT

The ventricular epithelium of the adult forebrain is a heterogeneous cell population that is a source of both quiescent and activated neural stem cells (qNSCs and aNSCs, respectively). We genetically targeted a subset of ventricle-contacting, glial fibrillary acidic protein (GFAP)-expressing cells, to study their involvement in qNSC/aNSC-mediated adult neurogenesis. Ventricle-contacting GFAP+ cells were lineage-traced beginning in early adulthood using adult brain electroporation and produced small numbers of olfactory bulb neuroblasts until at least 21 mo of age. Notably, electroporated GFAP+ neurogenic precursors were distinct from both qNSCs and aNSCs: they did not give rise to neurosphere-forming aNSCs in vivo or after extended passaging in vitro and they were not recruited during niche regeneration. GFAP+ cells with these properties included a FoxJ1+GFAP+ subset, as they were also present in an inducible FoxJ1 transgenic lineage-tracing model. Transiently overexpressing Mash1 increased the neurogenic output of electroporated GFAP+ cells in vivo, identifying them as a potentially recruitable population. We propose that the qNSC/aNSC lineage of the adult forebrain coexists with a distinct, minimally expanding subset of GFAP+ neurogenic precursors.


Subject(s)
Cerebral Ventricles/metabolism , Epithelium/metabolism , Gene Targeting , Nerve Growth Factors/genetics , Neural Stem Cells/metabolism , Prosencephalon/metabolism , Adult , Adult Stem Cells/metabolism , Animals , Biomarkers , Cell Differentiation/genetics , Fluorescent Antibody Technique , Gene Expression , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Humans , Mice , Mice, Transgenic , Nerve Growth Factors/metabolism , Neural Stem Cells/cytology , Neurogenesis/genetics , Neurons/cytology , Neurons/metabolism , Olfactory Bulb/cytology , Olfactory Bulb/metabolism , Stem Cell Niche/genetics
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