03797nas a2200853   4500000000100000000000100001008004100002260001200043653001700055653002100072653003000093653001500123653002000138100002100158700001300179700002800192700001400220700001700234700002000251700001600271700001800287700002300305700002100328700002500349700002400374700002000398700002500418700003000443700002400473700002800497700001400525700002500539700001100564700001700575700002400592700001900616700002100635700002100656700002600677700001700703700002100720700002100741700002300762700002400785700001800809700002000827700002200847700002300869700002100892700002400913700002200937700001900959700002600978700002301004700002201027700002501049700002201074700002401096700002701120700002401147700002101171700001901192700001801211700002101229700002101250700002001271700002301291245007601314856005501390300001201445490000801457520146401465022001402929       2024                            d  c2024-1110aCell biology10aData integration10aGastrointestinal Diseases10aImmunology10aTranscriptomics1 aAmanda J. Oliver1 aNi Huang1 aRaquel Bartolome-Casado1 aRuoyan Li1 aSimon Koplev1 aHogne R. Nilsen1 aMadelyn Moy1 aBatuhan Cakir1 aKrzysztof Polanski1 aVictoria Gudiño1 aElisa Melón-Ardanaz1 aDinithi Sumanaweera1 aDaniel Dimitrov1 aLisa Marie Milchsack1 aMichael E. B. FitzPatrick1 aNicholas M. Provine1 aJacqueline M. Boccacino1 aEmma Dann1 aAlexander V. Predeus1 aKen To1 aMartin Prete1 aJonathan A. Chapman1 aAndrea C. Masi1 aEmily Stephenson1 aJustin Engelbert1 aSebastian Lobentanzer1 aShani Perera1 aLaura Richardson1 aRakeshlal Kapuge1 aAnna Wilbrey-Clark1 aClaudia I. Semprich1 aSophie Ellams1 aCatherine Tudor1 aPhilomeena Joseph1 aAlba Garrido-Trigo1 aAna M. Corraliza1 aThomas R. W. Oliver1 aC. Elizabeth Hook1 aKylie R. James1 aKrishnaa T. Mahbubani1 aKourosh Saeb-Parsy1 aMatthias Zilbauer1 aJulio Saez-Rodriguez1 aMarte Lie Høivik1 aEspen S. Bækkevold1 aChristopher J. Stewart1 aJanet E. Berrington1 aKerstin B. Meyer1 aPaul Klenerman1 aAzucena Salas1 aMuzlifah Haniffa1 aFrode L. Jahnsen1 aRasa Elmentaite1 aSarah A. Teichmann00aSingle-cell integration reveals metaplasia in inflammatory gut diseases  uhttps://www.nature.com/articles/s41586-024-07571-1  a699-7070 v6353 aThe gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn’s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner’s glands. Although previously linked to mucosal healing4, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.  a1476-4687