Lysophosphatidic Acid Receptor Is a Functional Marker of Adult Hippocampal Precursor Cells

Stem Cell Reports. 2016 Apr 12;6(4):552-565. doi: 10.1016/j.stemcr.2016.03.002. Epub 2016 Mar 31.

Abstract

Here, we show that the lysophosphatidic acid receptor 1 (LPA1) is expressed by a defined population of type 1 stem cells and type 2a precursor cells in the adult mouse dentate gyrus. LPA1, in contrast to Nestin, also marks the quiescent stem cell population. Combining LPA1-GFP with EGFR and prominin-1 expression, we have enabled the prospective separation of both proliferative and non-proliferative precursor cell populations. Transcriptional profiling of the isolated proliferative precursor cells suggested immune mechanisms and cytokine signaling as molecular regulators of adult hippocampal precursor cell proliferation. In addition to LPA1 being a marker of this important stem cell population, we also show that the corresponding ligand LPA is directly involved in the regulation of adult hippocampal precursor cell proliferation and neurogenesis, an effect that can be attributed to LPA signaling via the AKT and MAPK pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Blotting, Western
  • Cell Proliferation*
  • Cell Separation
  • Cells, Cultured
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Profiling / methods
  • Gene Ontology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Lysophospholipids / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Running
  • Signal Transduction / drug effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*

Substances

  • Biomarkers
  • Lysophospholipids
  • Receptors, Lysophosphatidic Acid
  • Green Fluorescent Proteins
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • lysophosphatidic acid