FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency
Open accessAbstract
The stem cell niche houses and regulates stem cells by providing both physical contact and local factors that regulate stem cell identity. The stem cell niche also plays a role in integrating niche-local and systemic signals, thereby ensuring that the balance of stem cells meets the needs of the organism. However, it is not clear how these signals are merged within the niche. Nutrient-sensing insulin/FOXO signaling has been previously shown to directly control Notch activation in the Drosophila female germline stem cell (GSC) niche, which maintains the niche and GSC identity. Here, we demonstrate that FOXO directly activates transcription of fringe, a gene encoding a glycosyltransferase that modulates Notch glycosylation. Fringe facilitates Notch inactivation in the GSC niche when insulin signaling is low. We also show that the Notch ligand predominantly involved is GSC niche-derived Delta. These results reveal that FOXO-mediated regulation of fringe links the insulin and Notch signaling pathways in the GSC niche in response to nutrition, and emphasize that stem cells are regulated by complex interactions between niche-local and systemic signals.
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Nutrient-sensing pathways SIRT1, AMPK and FoxO may be molecular effectors of calorie restriction's benefits on stem cell activity.
“Signaling pathways related to nutrient sensing and uptake, such as SIRT1, AMPK and FoxO, may represent molecular effectors of the benefits of CR on stem cell activity113,114, although a complete understanding of how CR affects stem cell function must await further studies.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [114]
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- Authors
- Yang, S.-A., Wang, W.-D., Chen, C.-T., Tseng, C.-Y., Chen, Y.-N., & Hsu, H.-J.
- Affiliations
- Institute of Cellular and Organismic Biology, Academia Sinica (TW)
- National Chiayi University (TW)
- Institute of Molecular Biology, Academia Sinica (TW)
- Corresponding author
- Hsu, Hwei-Jan
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 382
- Issue
- 1
- Pages
- 124-135
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2096373575
- Cited by
- 37
- References
- 55
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 6 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 2 · 2014: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the Institute of Cellular and Organismic Biology, Academia Sinica, Taiwan (NSC 99-2311-B-001-023, 100-2311-B-001-016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- FOXO, fringe, germline stem cells, stem cell niche, insulin signaling, Notch signaling, Delta ligand, Drosophila, transcriptional regulation
- MeSH terms
- Animals, Base Sequence, Cell Count, Cell Nucleus, Drosophila melanogaster, Female, Germ Cells, Glycosylation, Insulin, Models, Biological, Molecular Sequence Data, Mutation, Promoter Regions, Genetic, Protein Binding, Receptor, Insulin, Transcription, Genetic, Zebrafish, Signal Transduction, N-Acetylglucosaminyltransferases, Drosophila Proteins, Forkhead Transcription Factors, Stem Cell Niche
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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