{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:54:52Z","timestamp":1791179692664,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the epithelial state associated with GART expression in ulcerative colitis (UC) and determine whether this association reflects a GART-specific program or a broader proliferative and purine-metabolic phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Four independent bulk transcriptomic cohorts were analyzed and synthesized by random-effects meta-analysis. Human colonic scRNA-seq datasets (GSE214695 and SCP259) were integrated, with principal comparisons repeated using donor-aware pseudobulk or mixed-effects approaches and adjustment for sequencing depth, gene detection, and cell-cycle covariates. GART detection was defined from raw counts and tested using alternative thresholds. Pseudotime, scTenifoldKnk, CellChat\/LIANA, and transcriptional-network analyses were used as exploratory analyses. Spatial transcriptomics (GSE189184), human colonic multiplex immunofluorescence, and acute DSS-induced colitis tissues were used for tissue-level localization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across the four bulk cohorts, GART expression showed an overall increase in UC (pooled Hedges\u2019 g = 0.743, 95% CI 0.239\u20131.248; P\u00a0=\u00a00.0183). In the single-cell atlas, GART detection localized preferentially to an ISC-like epithelial compartment, although the magnitude of the UC-associated detection difference varied between cohorts. Within UC ISC-like cells, donor-paired pseudobulk analyses identified proliferative and nucleotide-metabolic transcriptional differences associated with GART detection. Across the broader ISC-like epithelial atlas, donor-aware module analyses showed positive associations of GART detection with purine-biosynthesis, DNA-replication, DNA-repair, and mitotic programs, and these associations remained positive within cell-cycle strata. Comparison with other\n                      <jats:italic>de novo<\/jats:italic>\n                      purine-synthesis enzymes did not support a uniquely GART-specific alteration. Exploratory network analyses linked the GART-associated state to proliferative and nucleotide-metabolic programs but did not establish functional dependence. In seven independent spatial donors, the single-cell-derived epithelial program was consistently higher in GART-detected than GART-undetected epithelial regions (mean within-donor difference = 0.0262, 95% CI 0.0140\u20130.0407; exact P\u00a0=\u00a00.0156). Human tissue immunofluorescence further showed co-enrichment of GART with OLFM4-positive ISC-like, MYBL2\/Ki67-positive proliferative, and MIF\/CD74-associated inflammatory regions across the corresponding panel-specific participant sets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GART identifies a proliferative and purine-metabolic ISC-like epithelial state in UC but is not established as a specific driver of epithelial regeneration. The findings support an association between GART detection, nucleotide-demand programs, proliferative epithelial activity, and the inflammatory tissue context, providing a framework for future direct functional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1913904","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:31:19Z","timestamp":1791178279000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["GART expression is associated with a proliferative and purine-metabolic ISC-like epithelial state in ulcerative colitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinchen","family":"Chong","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"No. 1 Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Ding","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"No. 1 Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaze","family":"Ma","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Pan","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Endoscopy Center, The Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine)","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugen","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine","place":["Nanjing, China"]},{"name":"Jiangsu Province Key Laboratory of Tumor Systems Biology and Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicine in Prevention and Treatment of Tumor, The Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2025-2","article-title":"Pathway paradigms revealed from the genetics of inflammatory bowel disease","volume":"578","author":"Graham","year":"2020","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.10.020","article-title":"Understanding and preventing the global increase of inflammatory bowel 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