Pigment epithelium-derived factor is a niche signal for neural stem cell renewal.
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.
Ramírez-Castillejo
Carmen
C
Departamento de Biología Celular, Universidad de Valencia, Burjassot 46100, Spain.
Sánchez-Sánchez
Francisco
F
Andreu-Agulló
Celia
C
Ferrón
Sacri R
SR
Aroca-Aguilar
J Daniel
JD
Sánchez
Pilar
P
Mira
Helena
H
Escribano
Julio
J
Fariñas
Isabel
I
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004730:Endothelium, Vascular / Q000378:metabolism; D004805:Ependyma / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007276:Injections, Intraventricular; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor