RRC ID 47481
著者 Tseng CY, Kao SH, Wan CL, Cho Y, Tung SY, Hsu HJ.
タイトル Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche.
ジャーナル PLoS Genet
Abstract Stem cells have an innate ability to occupy their stem cell niche, which in turn, is optimized to house stem cells. Organ aging is associated with reduced stem cell occupancy in the niche, but the mechanisms involved are poorly understood. Here, we report that Notch signaling is increased with age in Drosophila female germline stem cells (GSCs), and this results in their removal from the niche. Clonal analysis revealed that GSCs with low levels of Notch signaling exhibit increased adhesiveness to the niche, thereby out-competing their neighbors with higher levels of Notch; adhesiveness is altered through regulation of E-cadherin expression. Experimental enhancement of Notch signaling in GSCs hastens their age-dependent loss from the niche, and such loss is at least partially mediated by Sex lethal. However, disruption of Notch signaling in GSCs does not delay GSC loss during aging, and nor does it affect BMP signaling, which promotes self-renewal of GSCs. Finally, we show that in contrast to GSCs, Notch activation in the niche (which maintains niche integrity, and thus mediates GSC retention) is reduced with age, indicating that Notch signaling regulates GSC niche occupancy both intrinsically and extrinsically. Our findings expose a novel role of Notch signaling in controlling GSC-niche adhesion in response to aging, and are also of relevance to metastatic cancer cells, in which Notch signaling suppresses cell adhesion.
巻・号 10(12)
ページ e1004888
公開日 2014-12-1
DOI 10.1371/journal.pgen.1004888
PII PGENETICS-D-14-01703
PMID 25521289
PMC PMC4270478
MeSH Aging Animals Bone Morphogenetic Proteins / physiology Cdh1 Proteins / metabolism Cell Adhesion* Cell Proliferation Drosophila Proteins / metabolism Drosophila Proteins / physiology* Drosophila melanogaster / cytology Female RNA-Binding Proteins / physiology Receptors, Notch / physiology* Signal Transduction Stem Cell Niche* Stem Cells / physiology*
IF 5.175
引用数 18
WOS 分野 GENETICS & HEREDITY
リソース情報
ショウジョウバエ 10853R-3