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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.

2016-07-03 | E-GEOD-68270 | biostudies-arrayexpress

Adult hippocampal neurogenesis in aged macaques and humans

Project description:We performed snRNA-seq of macaque hippocampal formation sample to investigate whether there is the existence of adult neural stem cells and adult hippocampal neurogenesis.

2022-06-29 | GSE163737 | GEO

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVitro_RRBS]

Project description:Dynamic DNA methylation controls gene-regulatory networks underlying cell fate specification. How DNA methylation patterns change during adult hippocampal neurogenesis and their relevance for the generation of new neurons from adult neural stem cells has, however, remained unknown. Here, we show that neurogenesis-associated de novo DNA methylation is critical for maturation and functional integration of adult-born hippocampal neurons. Cell stage-specific bisulfite sequencing revealed a pronounced gain of DNA methylation at neuronal enhancers, gene bodies and binding sites of pro-neuronal transcription factors during adult neurogenesis, which mostly correlated with transcriptional up-regulation of the associated loci. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells specifically impaired dendritic outgrowth and synaptogenesis of new neurons, resulting in impaired hippocampal excitability and specific deficits in hippocampus-dependent learning and memory. Our results highlight that, during adult neurogenesis, remodeling of neuronal methylomes is fundamental for proper hippocampal function.

2021-03-02 | GSE167954 | GEO

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [Dnmt_inVivo_RRBS]

2021-03-02 | GSE167953 | GEO

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis [scRNA-seq]

2021-03-02 | GSE167952 | GEO

Lysophosphatidic acid Shifts Metabolic and Transcriptional Landscapes to Induce a Novel Cellular State in Human Embryonic Stem Cells

Project description:Pluripotent stem cells can be maintained in a continuum of cellular states with distinct features. Exogenous lipid supplements are commonly utilized to shift the balance of global metabolism relieving the dependence on de novo lipogenesis. However, it is largely unexplored how specific lipid components regulate metabolism and pluripotency state. In this study, we investigate the impact of lipid supplements on human embryonic stem cells (hESCs), and report that signaling lipid lysophosphatidic acid (LPA) is the key component to shift the metabolic landscape in lipid supplement AlbuMAX. Although the maintenance of ERK phosphorylation and primed pluripotency is independent of exogenous lipids, LPA increases ERK phosphorylation, especially upon niche disintegration. We further demonstrate that LPA leads to distinctive transcriptome profile that is not associated with de novo lipogenesis. We also show that LPA causes unique and reversible phenotypes in cell cycle, morphology and mitochondria. This study reveals an LPA -induced primed state that allow people to drastically alter cell physiology for basic research and stem cell applications with hESCs.

2022-03-08 | GSE198007 | GEO

A fatty acid oxidation-dependent metabolic shift regulates adult neural stem cell quiescence

Project description:Adult hippocampal neurogenesis is important for certain forms of cognition and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. However, how this balance is regulated remains poorly understood. Here we show that the rate of fatty acid oxidation (FAO) defines quiescence vs. proliferation in NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, experimental manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity.

2019-11-15 | PXD005598 | Pride

Human gingival fibroblasts: control vs. lysophosphatidic acid (LPA 18:1)-treated

Project description:Transcriptional profiling of pass 2 primary human gingival fibroblasts (GF) comparing control untreated GF with GF treated with LPA 18:1 for 2h or 8h. The goal of this study was to determine the effects of LPA 18:1 on global GF gene expression. Three-condition experiment, GF vs. LPA-treated (2h, 8h) GF cells. Biological replicates: 3 control replicates, 3 LPA-treated replicates.

2014-05-12 | E-GEOD-57496 | biostudies-arrayexpress

Single-cell RNA-seq with Waterfall Reveals Molecular Cascades underlying Adult Hippocampal Neurogenesis

Project description:Somatic stem cells contribute to tissue ontogenesis, homeostasis, and regeneration through sequential processes. Systematic molecular analysis of stem cell behavior is challenging because classic approaches cannot resolve cellular heterogeneity or capture developmental dynamics. Here we provide a comprehensive resource of single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny. We further developed Waterfall, a bioinformatic suite, to statistically quantify singe-cell gene expression along de novo reconstructed continuous developmental trajectory. Our study reveals molecular signatures of qNSCs, characterized by high niche signaling integration and low protein translation capacity. Our analyses further delineate molecular cascades underlying adult qNSC activation and neurogenesis initiation, exemplified by decreased extrinsic signaling capacity, primed translational machinery, and regulatory switches in transcription factors, metabolism, and energy sources. Our study reveals the molecular continuum underlying adult neurogenesis and illustrates how Waterfall can be used for single-cell omics analyses of various continuous biological processes. Single-cell transcriptomes of adult hippocampal quiescent neural stem cells (qNSCs) and their immediate progeny.

2015-08-30 | E-GEOD-71485 | biostudies-arrayexpress

Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases

Project description:Lysophosphatidic acid (LPA) acts through high-affinity G protein-coupled receptors to mediate a plethora of physiological and pathological activities associated with tumorigenesis. LPA receptors and autotaxin (ATX/LysoPLD), the primary enzyme producing LPA, are aberrantly expressed in multiple cancer lineages. However, the role of ATX and LPA receptors in the initiation and progression of breast cancer has not been evaluated. We demonstrate that expression of ATX or each edg family LPA receptor in mammary epithelium of transgenic mice is sufficient to induce a high frequency of late-onset, estrogen receptor (ER)-positive, invasive, and metastatic mammary cancer. Thus, ATX and LPA receptors can contribute to the initiation and progression of breast cancer.

2009-06-11 | GSE15263 | GEO

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