{"doi":"10.1126/sciadv.adi2671","title":"Stem cell mTOR signaling directs region-specific cell fate decisions during intestinal nutrient adaptation","abstract":"<jats:p>The adult intestine is a regionalized organ, whose size and cellular composition are adjusted in response to nutrient status. This involves dynamic regulation of intestinal stem cell (ISC) proliferation and differentiation. How nutrient signaling controls cell fate decisions to drive regional changes in cell-type composition remains unclear. Here, we show that intestinal nutrient adaptation involves region-specific control of cell size, cell number, and differentiation. We uncovered that activation of mTOR complex 1 (mTORC1) increases ISC size in a region-specific manner. mTORC1 activity promotes Delta expression to direct cell fate toward the absorptive enteroblast lineage while inhibiting secretory enteroendocrine cell differentiation. In aged flies, the ISC mTORC1 signaling is deregulated, being constitutively high and unresponsive to diet, which can be mitigated through lifelong intermittent fasting. In conclusion, mTORC1 signaling contributes to the ISC fate decision, enabling regional control of intestinal cell differentiation in response to nutrition.</jats:p>","journal":"Science Advances","year":2024,"id":681097,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1779513,"name":"Arto Viitanen","orcid":"0000-0002-0197-4427","position":1,"is_corresponding":false},{"id":1779515,"name":"Gaia Fabris","orcid":"0000-0003-3453-082X","position":2,"is_corresponding":false},{"id":1779516,"name":"Tetiana Strutynska","orcid":"0000-0003-2854-1303","position":3,"is_corresponding":false},{"id":666276,"name":"Jerome Korzelius","orcid":"0000-0002-8443-0192","position":4,"is_corresponding":false},{"id":1352658,"name":"Ville Hietakangas","orcid":"0000-0002-9900-7549","position":5,"is_corresponding":false},{"id":1779510,"name":"Jaakko Mattila","orcid":"0000-0002-4064-2791","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Stem cell mTOR signaling directs region-specific cell fate decisions during intestinal nutrient adaptation","abstract":"<jats:p>The adult intestine is a regionalized organ, whose size and cellular composition are adjusted in response to nutrient status. This involves dynamic regulation of intestinal stem cell (ISC) proliferation and differentiation. How nutrient signaling controls cell fate decisions to drive regional changes in cell-type composition remains unclear. Here, we show that intestinal nutrient adaptation involves region-specific control of cell size, cell number, and differentiation. We uncovered that activation of mTOR complex 1 (mTORC1) increases ISC size in a region-specific manner. mTORC1 activity promotes Delta expression to direct cell fate toward the absorptive enteroblast lineage while inhibiting secretory enteroendocrine cell differentiation. In aged flies, the ISC mTORC1 signaling is deregulated, being constitutively high and unresponsive to diet, which can be mitigated through lifelong intermittent fasting. In conclusion, mTORC1 signaling contributes to the ISC fate decision, enabling regional control of intestinal cell differentiation in response to nutrition.</jats:p>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38335286","pmcid":"PMC10857434","openalex_id":"https://openalex.org/W4391677406","authors":[],"funders":[{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF22OC0078419","title":null}],"total_grants":1,"fwci":3.7734,"citation_percentile":0.94465753,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":14},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.adi2671?download=true","host_type":"journal"},{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.adi2671?download=true","host_type":"publisher"},{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.adi2671","host_type":"publisher"},{"url":"https://doi.org/10.1126/sciadv.adi2671","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38335286","host_type":"repository"},{"url":"https://doi.org/10.1126/sciadv.adi2671>)","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10857434","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10857434/pdf/sciadv.adi2671.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10857434","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10857434?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Genetics, Aging, and Longevity in Model Organisms","Invertebrate Immune Response Mechanisms","CRISPR and Genetic Engineering","Cell Differentiation","Cell Lineage","Cell Proliferation","Intestinal Mucosa","Intestines","Mechanistic Target of Rapamycin Complex 1","Nutrients","Stem Cells","TOR Serine-Threonine Kinases","Drosophila"],"mesh_terms":["Mechanistic Target of Rapamycin Complex 1","Nutrients","Cell Differentiation","Drosophila","Intestinal Mucosa","Intestines","Stem Cells","Cell Lineage","Cell Proliferation","TOR Serine-Threonine Kinases"],"keywords":["mTORC1","Cell fate determination","Cell biology","Biology","Nutrient sensing","PI3K/AKT/mTOR pathway","Signal transduction","Adaptation (eye)","Cellular differentiation","Cell","Stem cell","Cell growth","Transcription factor","Gene","Neuroscience","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T16:56:19.155388Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}