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Lysophosphatidic acid receptor expression identifies a pure population of adult hippocampal stem cells with an immune cell-related transcriptional profile

ABSTRACT: Lysophosphatidic acid receptor 1 (LPA1) is a phospholipid which has been linked to adult hippocampal neurogenesis and learning deficits. Here we investigated whether LPA acts directly on the hippocampal stem cells and whether LPA1 could be a functional marker for their prospective isolation. Our results reveal that exogenous LPA increases precursor potential in vitro and net neurogenesis in vivo, an effect that is mediated by Akt activation. Using a mouse reporter line, immunohistochemistry and flow cytometry followed by in vitro cell culture, we show that, in contrast to the subventricular zone, neural precursor cells in the adult mouse dentate gyrus express LPA1-GFP. Fluorescence-activated cell sorting for LPA1-GFP in combination with Prominin-1 and epidermal growth factor receptor expression allowed the efficient isolation of a very pure population of hippocampal stem cells. Transcriptional analysis revealed a profile suggesting immune response and cytokine signaling as molecular regulators of adult hippocampal neural stem cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE68270 | GEO | 2016/01/01

SECONDARY ACCESSION(S): PRJNA282345

REPOSITORIES: GEO

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Lysophosphatidic acid receptor expression identifies a pure population of adult hippocampal stem cells with an immune cell-related transcriptional profile

Project description:Lysophosphatidic acid receptor 1 (LPA1) is a phospholipid which has been linked to adult hippocampal neurogenesis and learning deficits. Here we investigated whether LPA acts directly on the hippocampal stem cells and whether LPA1 could be a functional marker for their prospective isolation. Our results reveal that exogenous LPA increases precursor potential in vitro and net neurogenesis in vivo, an effect that is mediated by Akt activation. Using a mouse reporter line, immunohistochemistry and flow cytometry followed by in vitro cell culture, we show that, in contrast to the subventricular zone, neural precursor cells in the adult mouse dentate gyrus express LPA1-GFP. Fluorescence-activated cell sorting for LPA1-GFP in combination with Prominin-1 and epidermal growth factor receptor expression allowed the efficient isolation of a very pure population of hippocampal stem cells. Transcriptional analysis revealed a profile suggesting immune response and cytokine signaling as molecular regulators of adult hippocampal neural stem cells. RNA from cells sorted (FACS) from the dentate gyrus of adult LPA1-GFP (lysophosphatidic acid receptor) reporter mice. Sorting was based on the markers EGFR (Egfr), LPA1 (Lpar1) and Prominin1 (Prom1). From each of 4 replicates, 3 populations (stem cells, progenitor cells, niche cells) were sequenced.

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