Nature Neuroscience 9, 331 - 339 (2006)
Published online: 19 February 2006; | doi:10.1038/nn1657
Pigment epithelium–derived factor is a niche signal for neural stem cell renewalCarmen Ramírez-Castillejo1, 3, 4, Francisco Sánchez-Sánchez2, 4, Celia Andreu-Agulló1, 4, Sacri R Ferrón1, 4, J Daniel Aroca-Aguilar2, Pilar Sánchez1, 3, Helena Mira1, 3, Julio Escribano2
& Isabel Fariñas1, 31
Departamento de Biología Celular, Universidad de Valencia, Burjassot 46100, Spain. 2
Área de Genética, Facultad de Medicina and Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha (UCLM), Albacete 02006, Spain. 3
Present addresses: Laboratorio de Oncología Molecular, Facultad de Medicina and CRIB, UCLM (C.R.-C.) and Unidad Mixta CIPF-UVEG (Centro de Investigación Príncipe Felipe-Universidad de Valencia Estudio General) and Departamento de Biología Celular, Centro de Investigación Príncipe Felipe, Departamento de Biología Celular, Universidad de Valencia, Burjassot 46100, Spain (P.S., H.M. & I.F.). 4
These authors contributed equally to this work.
Correspondence should be addressed to Isabel Fariñas isabel.farinas@uv.es Adult stem cells are characterized by self-renewal and multilineage differentiation, and these properties seem to be regulated by signals from adjacent differentiated cell types and by extracellular matrix molecules, which collectively define the stem cell "niche." Self-renewal is essential for the lifelong persistence of stem cells, but its regulation is poorly understood. In the mammalian brain, neurogenesis persists in two germinal areas, the subventricular zone (SVZ) and the hippocampus, where continuous postnatal neuronal production seems to be supported by neural stem cells (NSCs). Here we show that pigment epithelium–derived factor (PEDF) is secreted by components of the murine SVZ and promotes self-renewal of adult NSCs in vitro. In addition, intraventricular PEDF infusion activated slowly dividing stem cells, whereas a blockade of endogenous PEDF decreased their cycling. These data demonstrate that PEDF is a niche-derived regulator of adult NSCs and provide evidence for a role for PEDF protein in NSC maintenance.
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