{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:48:03Z","timestamp":1782280083777,"version":"3.54.5"},"posted":{"date-parts":[[2025,2,16]]},"group-title":"Cell Biology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A critical question in physiology is understanding how tissues adapt and alter their cellular composition in response to dietary cues. The mammalian small intestine, a vital digestive organ that absorbs nutrients, is maintained by rapidly renewing Lgr5\n                  <jats:sup>+<\/jats:sup>\n                  intestinal stem cells (ISCs) at the intestinal crypt base. While Lgr5\n                  <jats:sup>+<\/jats:sup>\n                  ISCs drive intestinal adaptation by altering self-renewal and differentiation divisions in response to diverse diets such as high-fat diets and fasting regimens, little is known about how micronutrients, particularly amino acids, instruct Lgr5\n                  <jats:sup>+<\/jats:sup>\n                  ISC fate decisions to control intestinal homeostasis and repair after injury. Here, we demonstrate that cysteine, an essential amino acid, enhances the ability of Lgr5\n                  <jats:sup>+<\/jats:sup>\n                  ISCs to repair intestinal injury. Mechanistically, the effects of cysteine on ISC-driven repair are mediated by elevated IL-22 from intraepithelial CD8\u03b1\u03b2\n                  <jats:sup>+<\/jats:sup>\n                  T cells. These findings highlight how coupled cysteine metabolism between ISCs and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells augments intestinal stemness, providing a dietary approach that exploits ISC and immune cell crosstalk for ameliorating intestinal damage.\n                <\/jats:p>","DOI":"10.1101\/2025.02.15.638423","type":"posted-content","created":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T08:40:23Z","timestamp":1739695223000},"source":"Crossref","is-referenced-by-count":0,"title":["Dietary cysteine enhances intestinal stemness via CD8\n                  <sup>+<\/sup>\n                  T cell-derived IL-22"],"prefix":"10.64898","author":[{"given":"Fangtao","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E.S.","family":"Shay","sequence":"additional","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna Ten","family":"Hoeve","sequence":"additional","affiliation":[{"name":"UCLA Metabolomics Center, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenning","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heaji","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumeet","family":"Solanki","sequence":"additional","affiliation":[{"name":"Molecular & Integrative Physiology Department and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yatrik M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Molecular & Integrative Physiology Department and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Agudo","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"},{"name":"Department of Immunology, Harvard Medical School, Boston, MA 02215, USA"},{"name":"Ludwig Center at Harvard, Boston, MA 02215, USA"},{"name":"Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer H.","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, MIT, Cambridge, MA 02139, USA"},{"name":"Department of Pathology, Beth Israel Deaconess Medical Center and Massachusetts General Hospital Boston and Harvard Medical School, Boston, MA 02114, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041110103756000_2025.02.15.638423v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11163"},{"key":"2026041110103756000_2025.02.15.638423v1.2","unstructured":"Imada, S. et al. Short-term post-fast refeeding enhances intestinal stemness via polyamines. Nature, 1\u201310 (2024)."},{"key":"2026041110103756000_2025.02.15.638423v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature17173"},{"key":"2026041110103756000_2025.02.15.638423v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3593"},{"key":"2026041110103756000_2025.02.15.638423v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.04.001"},{"key":"2026041110103756000_2025.02.15.638423v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.12.017"},{"key":"2026041110103756000_2025.02.15.638423v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.07.048"},{"key":"2026041110103756000_2025.02.15.638423v1.8","doi-asserted-by":"crossref","unstructured":"Mana, M. D. et al. High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity. 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