Enhanced Fitness of Adult Spermatogonial Stem Cells Bearing a Paternal Age-Associated FGFR2 Mutation

• DOI: 10.1016/j.stemcr.2014.06.007
• Publication Date: 2014-07-17T15:55:13Z
• Authors: Laura A. Martin; Nicholas Assif; Moses Gilbert; Dinali Wijewarnas...; Marco Seandel
• Keywords: Child bearing

Pathogenic de novo mutations increase with fathers' age and could be amplified through competition between genetically distinct subpopulations of spermatogonial stem cells (SSCs). Here, we tested the fitness SSCs bearing wild-type human FGFR2 or an Apert syndrome mutant, (S252W), to provide experimental evidence for SSC competition. The S252W allele conferred enhanced FGFR2-mediated signaling, particularly at very low concentrations ligand, also subtle changes in gene expression. Mutant exhibited improved competitiveness vitro increased cell activity vivo upon transplantation. advantage only occurred fibroblast growth factor (FGF), was independent FGF-driven proliferation, accompanied by response glial line-derived neurotrophic (GDNF). Our studies a paternal age-associated mutation. model will useful interrogating other candidate future reveal mechanisms disease risk.