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Defects in subventricular zone pigmented epithelium‐derived factor niche signaling in the senescence‐accelerated mouse prone‐8
Author(s) -
CastroGarcia Paola,
DíazMoreno María,
GilGas Carmen,
FernándezGómez Francisco J.,
HonrubiaGómez Paloma,
ÁlvarezSimón Carmen Belén,
SánchezSánchez Francisco,
Cano Juan Carlos Castillo,
Almeida Francisco,
Blanco Vicente,
Jordán Joaquín,
Mira Helena,
RamírezCastillejo Carmen
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-244442
Subject(s) - senescence , epithelium , microbiology and biotechnology , subventricular zone , niche , biology , stem cell , genetics , ecology , progenitor cell
We studied potential changes in the sub‐ventricular zone (SVZ) stem cell niche of the senescence‐accelerated mouse prone‐8 (SAM‐P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label‐retaining stem cells in the SAM‐P8 SVZ compared with the SAM‐Resistant 1 (SAM‐R1) control strain. We also found that in SAM‐P8 niche signaling is attenuated and the stem cell pool is less responsive to the self‐renewal niche factor pigmented epithelium‐derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM‐P8 SVZ niche; however, SAM‐P8 stem cells present a significant expression decrease of patatin‐like phospholipase domain containing 2, a receptor for PEDF (PNPLA2‐PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR‐PEDF) receptor. We observed changes in self‐renewal related genes (hairy and enhancer of split 1 ( Hes1 ), hairy and enhancer of split 1 ( Hes5 ), Sox2 ] and report that although these genes are down‐regulated in SAM‐P8, differentiation genes ( Pax6 ) are up‐regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down‐regulation of telomeric repeat binding factor 1 ( Terf1 ) expression was observed in SAM‐P8 at young age periods. Differences between these 2 models, SAM‐P8 and SAM‐R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self‐renewal at a very young age, which could be involved in the premature senescence observed in the SAM‐P8 model.—Castro‐Garcia, P., Díaz‐Moreno, M., Gil‐Gas, C., Fernández‐Gómez, F. J., Honrubia‐Gómez, P., Álvarez‐Simón, C. B., Sánchez‐Sánchez, F., Cano. J. C. C., Almeida, F., Blanco. V., Jordán, J. Mira, H., Ramírez‐Castillejo, C. Defects in sub‐ventricular zone pigmented epithelium‐derived factor niche signaling in the senescence‐accelerated mouse prone‐8. FASEB J. 29, 1480‐1492 (2015). www.fasebj.org