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

• LPA1-GFP+ allows the prospective isolation of hippocampal precursor cells
• Method for separation of proliferative from non-proliferative precursor cells
• Proliferative precursor cells have a unique immune-cell-like transcriptional profile
• LPA increases in vivo hippocampal neurogenesis via the LPA1-AKT and MAPK pathways

SummaryHere, 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.