%0 Journal Article
%T Soluble amyloid precursor protein: a novel proliferation factor of adult progenitor cells of ectodermal and mesodermal origin
%A Michael P Demars
%A Amelia Bartholomew
%A Zuzana Strakova
%A Orly Lazarov
%J Stem Cell Research & Therapy
%D 2011
%I BioMed Central
%R 10.1186/scrt77
%X sAPP¦Á and ¦Á-secretase activities were determined in neural progenitor cells (NPCs), mesenchymal stem cells (MSC) and human decidua parietalis placenta stem cells (hdPSC). Inhibition of ¦Á-secretase was achieved by treatment with the matrixmetalloproteinase inhibitor GM6001, and proliferation was determined using clonogenic and immunocytochemical analysis of cell-lineage markers. Recovery of proliferation was achieved by supplementing GM6001-treated cells with recombinant soluble APP¦Á. Expression of APP and its cellular localization in the subventricular zone was determined by Western blot and immunohistochemical analyses of APP wild type and knockout tissue. Alterations in pERK and pAKT expression as a function of soluble APP¦Á production and activity in NPCs were determined by Western blot analysis.Here we show that sAPP¦Á is a proliferation factor of adult NPCs, MSCs and hdpPSC. Inhibition of ¦Á-secretase activity reduces proliferation of these stem cell populations in a dose-dependent manner. Stem cell proliferation can be recovered by the addition of sAPP¦Á in a dose-dependent manner, but not of media depleted of sAPP¦Á. Importantly, sAPP¦Á operates independently of the prominent proliferation factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), but in association with ERK signaling and MAP-kinase signaling pathways. Levels of sAPP¦Á and putative ¦Á-secretase, ADAM10, are particularly high in the subventricular zone of adult mice, suggesting a role for sAPP¦Á in regulation of NPCs in this microenvironment.These results determine a physiological function for sAPP¦Á and identify a new proliferation factor of progenitor cells of ectodermal and mesodermal origin. Further, our studies elucidate a potential pathway for sAPP¦Á signaling through MAP kinase activation.Amyloid precursor proteins (APPs) comprise a family of evolutionarily conserved single-pass type I transmembrane glycoproteins of an unknown physiological function. In mammals, that family i
%U http://stemcellres.com/content/2/4/36