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Using mouse lineage tracing, immunohistochemistry, and single-cell sequencing, we have identified a rare, non-CBC, T-cell factor 4 lineage-negative (\n                  <jats:italic>Tcf4<\/jats:italic>\n                  Lin-) stem cell population that gives rise to secretory and absorptive precursors. Following endoscopic biopsy-induced injury,\n                  <jats:italic>Tcf4<\/jats:italic>\n                  Lin- stem cells are recruited to the wound bed and to the site of expanding crypts and function in barrier restoration and wound repair. We show that in a\n                  <jats:italic>Tcf4<\/jats:italic>\n                  -haploinsufficient background, the\n                  <jats:italic>Tcf4<\/jats:italic>\n                  Lin-, but not the\n                  <jats:italic>Tcf4<\/jats:italic>\n                  Lin+, cell population represents the cell of origin for colon tumors driven by deletion of\n                  <jats:italic>Apc<\/jats:italic>\n                  . Our results provide a foundation for understanding\n                  <jats:italic>Apc<\/jats:italic>\n                  -allele-specific differences during colon tumorigenesis and identify a new stem-cell population that may prove valuable in the treatment of diseases caused by intestinal barrier homeostasis defects.\n                <\/jats:p>","DOI":"10.64898\/2026.03.17.712502","type":"posted-content","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T18:35:19Z","timestamp":1773858919000},"source":"Crossref","is-referenced-by-count":0,"title":["A Rare T-Cell Factor 4 Lineage-negative Epithelial Stem Cell Supports Wound Repair and APC-deletion-induced Colon Tumorigenesis"],"prefix":"10.64898","author":[{"given":"Annika V.","family":"Thorpe","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA"},{"name":"Huntsman Cancer Institute, University of 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