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• W2016075650 abstract "The nutritional status of an organism can greatly impact the function and behavior of stem and progenitor cells [1Mihaylova M.M. Sabatini D.M. Yilmaz O.H. Dietary and metabolic control of stem cell function in physiology and cancer.Cell Stem Cell. 2014; 14: 292-305Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. However, the regulatory circuits that inform these cells about the dietary environment remain to be elucidated. Newly hatched C. elegans larvae (L1s) halt development in “L1 arrest” or “L1 diapause” until ample food is encountered and triggers stem and progenitor cells to exit from quiescence [2Baugh L.R. To grow or not to grow: nutritional control of development during Caenorhabditis elegans L1 arrest.Genetics. 2013; 194: 539-555Crossref PubMed Scopus (135) Google Scholar]. The insulin/insulin-like growth factor signaling (IIS) pathway plays a key role in this reactivation [3Fukuyama M. Rougvie A.E. Rothman J.H. C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline.Curr. Biol. 2006; 16: 773-779Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 4Baugh L.R. Sternberg P.W. DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest.Curr. Biol. 2006; 16: 780-785Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar], but its site(s) of action have not been elucidated nor have the nutrient molecule(s) that stimulate the pathway been identified. By tissue-specifically modulating the activity of its components, we demonstrate that the IIS pathway acts in the hypodermis to regulate nutrition-responsive reactivation of neural and mesodermal progenitor cells. We identify ethanol, a likely component of the natural Caenorhabditis habitat, and amino acids as nutrients that synergistically reactivate somatic progenitor cells and upregulate expression of insulin-like genes in starved L1 larvae. The hypodermis likely senses the availability of amino acids because forced activation of the amino-acid-responsive Rag-TORC1 (target of rapamycin complex 1) pathway in this tissue can also release somatic progenitor cell quiescence in the presence of ethanol. Finally, there appears to be crosstalk between the IIS and Rag-TORC1 pathways because constitutive activation of the IIS pathway requires Rag to promote reactivation. This work demonstrates that ethanol and amino acids act as dietary cues via the IIS and Rag-TORC1 pathways in the hypodermis to coordinately control progenitor cell behavior." @default.
• W2016075650 created "2016-06-24" @default.
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• W2016075650 date "2015-05-01" @default.
• W2016075650 modified "2023-10-01" @default.
• W2016075650 title "The C. elegans Hypodermis Couples Progenitor Cell Quiescence to the Dietary State" @default.
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• W2016075650 doi "https://doi.org/10.1016/j.cub.2015.03.016" @default.
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