Skip to content
naulon

No retraction, correction or concern found when last checked on Nov 1, 2026.

Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn’s Disease

Rasa Elmentaite, Alexander D.B. Ross, Kenny Roberts and 11 more

Developmental Cell · 2020 · CC BY

doi:10.1101/2020.02.06.937110

Abstract

Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map of the developing human intestine at 6-10 weeks post-conception. Our analysis reveals the transcriptional profile of cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated cell subsets via the generation of LGR5-expressing stem cells and receive signals from surrounding mesenchymal cells. Furthermore, we draw parallels between the transcriptomes of ex vivo tissues and in vitro fetal organoids, revealing the maturation of organoid cultures in a dish. Lastly, we compare scRNA-seq profiles from pediatric Crohn's disease epithelium alongside matched healthy controls to reveal disease-associated changes in the epithelial composition. Contrasting these with the fetal profiles reveals the re-activation of fetal transcription factors in Crohn's disease. Our study provides a resource available at www.gutcellatlas.org, and underscores the importance of unraveling fetal development in understanding disease.

References 89

  1. 1.

    Alimperti S., Andreadis S.T. CDH2 and CDH11 act as regulators of stem cell fate decisions. Stem Cell Res. 2015;14:270-282.

    Not in our library10.1016/j.scr.2015.02.002

  2. 2.
  3. 3.

    Barker N., Huls G., Korinek V., Clevers H. Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium. Am. J. Pathol. 1999;154:29-35.

    Not in our library10.1016/s0002-9440(10)65247-9

  4. 4.

    Barker N., van Es J.H., Kuipers J., Kujala P., van den Born M., Cozijnsen M., Haegebarth A., Korving J., Begthel H., Peters P.J., Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003-1007.

    Not in our library10.1038/nature06196

  5. 5.

    Bayraktar O.A., Bartels T., Holmqvist S., Kleshchevnikov V., Martirosyan A., Polioudakis D., Ben Haim L., Young A.M.H., Batiuk M.Y., Prakash K. Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat. Neurosci. 2020;23:500-509.

    Not in our library10.1038/s41593-020-0602-1

  6. 6.

    Becht E., McInnes L., Healy J., Dutertre C.A., Kwok I.W.H., Ng L.G., Ginhoux F., Newell E.W. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 2018.

    Not in our library10.1038/nbt.4314

  7. 7.

    Begue B., Wajant H., Bambou J.C., Dubuquoy L., Siegmund D., Beaulieu J.F., Canioni D., Berrebi D., Brousse N., Desreumaux P. Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions. Gastroenterology. 2006;130:1962-1974.

    Not in our library10.1053/j.gastro.2006.03.022

  8. 8.

    Bergen V., Lange M., Peidli S., Wolf F.A., Theis F.J. Generalizing RNA velocity to transient cell states through dynamical modeling. Nat. Biotechnol. 2020.

    Not in our library10.1038/s41587-020-0591-3

  9. 9.

    Bo L., Fu H., Yang J. Comprehensive analysis of gene expression profiles provides insight into the pathogenesis of Crohn’s disease. Mol. Med. Rep. 2018;18:2643-2650.

    Not in our library10.3892/mmr.2018.9267

  10. 10.

    Boucherat O., Landry-Truchon K., Bérubé-Simard F.A., Houde N., Beuret L., Lezmi G., Foulkes W.D., Delacourt C., Charron J., Jeannotte L. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis. Development. 2015;142:2981-2995.

    Not in our library10.1242/dev.120469

  11. 11.

    Bush B.M., Brock A.T., Deng J.A., Nelson R.A., Sumter T.F. The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer. Cell Biochem. Funct. 2013;31:228-236.

    Not in our library10.1002/cbf.2876

  12. 12.

    Chin A.M., Hill D.R., Aurora M., Spence J.R. Morphogenesis and maturation of the embryonic and postnatal intestine. Semin. Cell Dev. Biol. 2017;66:81-93.

    Not in our library10.1016/j.semcdb.2017.01.011

  13. 13.

    Chin A.M., Tsai Y.H., Finkbeiner S.R., Nagy M.S., Walker E.M., Ethen N.J., Williams B.O., Battle M.A., Spence J.R. A dynamic WNT/β-catenin signaling environment leads to WNT-independent and WNT-dependent proliferation of embryonic intestinal progenitor cells. Stem Cell Rep. 2016;7:826-839.

    Not in our library10.1016/j.stemcr.2016.09.004

  14. 14.

    Cilieborg M.S., Boye M., Sangild P.T. Bacterial colonization and gut development in preterm neonates. Early Hum. Dev. 2012;88:S41-S49.

    Not in our library10.1016/j.earlhumdev.2011.12.027

  15. 15.

    Czerwinski M., Holloway E.M., Tsai Y.-H., Wu A., Yu Q., Wu J., Walton K.D., Sweet C., Childs C. In vitro and in vivo development of the human intestinal niche at single cell resolution. bioRxiv. 2020.

    Not in our library10.1101/2020.01.31.928788

  16. 16.

    de Lange K.M., Moutsianas L., Lee J.C., Lamb C.A., Luo Y., Kennedy N.A., Jostins L., Rice D.L., Gutierrez-Achury J., Ji S.-G. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat. Genet. 2017;49:256-261.

    Not in our library10.1038/ng.3760

  17. 17.

    Du L., Kim J.J., Shen J., Chen B., Dai N. KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis. Oncotarget. 2017;8:22175-22186.

    Not in our library10.18632/oncotarget.14549

  18. 18.

    Dupaul-Chicoine J., Dagenais M., Saleh M. Crosstalk between the intestinal microbiota and the innate immune system in intestinal homeostasis and inflammatory bowel disease. Inflam. Bowel Dis. 2013;19:2227-2237.

    Not in our library10.1097/mib.0b013e31828dcac7

  19. 19.

    Efremova M., Vento-Tormo M., Teichmann S.A., Vento-Tormo R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 2020;15:1484-1506.

    Not in our library10.1038/s41596-020-0292-x

  20. 20.

    Ellinghaus D., Zhang H., Zeissig S., Lipinski S., Till A., Jiang T., Stade B., Bromberg Y., Ellinghaus E., Keller A. Association between variants of PRDM1 and NDP52 and Crohn’s disease, based on exome sequencing and functional studies. Gastroenterology. 2013;145:339-347.

    Not in our library10.1053/j.gastro.2013.04.040

  21. 21.
  22. 22.

    Gao S., Yan L., Wang R., Li J., Yong J., Zhou X., Wei Y., Wu X., Wang X., Fan X. Publisher Correction: tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nat. Cell Biol. 2018;20:1227.

    Not in our library10.1038/s41556-018-0165-5

  23. 23.

    Gersemann M., Becker S., Kübler I., Koslowski M., Wang G., Herrlinger K.R., Griger J., Fritz P., Fellermann K., Schwab M. Differences in goblet cell differentiation between Crohn’s disease and ulcerative colitis. Differentiation. 2009;77:84-94.

    Not in our library10.1016/j.diff.2008.09.008

  24. 24.

    Geske M.J., Zhang X., Patel K.K., Ornitz D.M., Stappenbeck T.S. FGF9 signaling regulates small intestinal elongation and mesenchymal development. Development. 2008;135:2959-2968.

    Not in our library10.1242/dev.020453

  25. 25.

    Grosse A.S., Pressprich M.F., Curley L.B., Hamilton K.L., Margolis B., Hildebrand J.D., Gumucio D.L. Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis. Development. 2011;138:4423-4432.

    Not in our library10.1242/dev.065789

  26. 26.

    Guiu J., Hannezo E., Yui S., Demharter S., Ulyanchenko S., Maimets M., Jørgensen A., Perlman S., Lundvall L., Mamsen L.S. Tracing the origin of adult intestinal stem cells. Nature. 2019;570:107-111.

    Not in our library10.1038/s41586-019-1212-5

  27. 27.

    Harper J., Mould A., Andrews R.M., Bikoff E.K., Robertson E.J. The transcriptional repressor Blimp1/Prdm1 regulates postnatal reprogramming of intestinal enterocytes. Proc. Natl. Acad. Sci. USA. 2011;108:10585-10590.

    Not in our library10.1073/pnas.1105852108

  28. 28.

    Horvath B., Liu G., Wu X., Lai K.K., Shen B., Liu X. Overexpression of p53 predicts colorectal neoplasia risk in patients with inflammatory bowel disease and mucosa changes indefinite for dysplasia. Gastroenterol. Rep. 2015;3:344-349.

    Not in our library10.1093/gastro/gov022

  29. 29.

    Ito K., Yamazaki S., Yamamoto R., Tajima Y., Yanagida A., Kobayashi T., Kato-Itoh M., Kakuta S., Iwakura Y., Nakauchi H., Kamiya A. Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice. J. Biol. Chem. 2014;289:29892-29911.

    Not in our library10.1074/jbc.m114.580084

  30. 30.

    Kaestner K.H. The intestinal stem cell niche: a central role for Foxl1-expressing subepithelial Telocytes. Cell. Mol. Gastroenterol. Hepatol. 2019;8:111-117.

    Not in our library10.1016/j.jcmgh.2019.04.001

  31. 31.

    Karlsson L., Lindahl P., Heath J.K., Betsholtz C. Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development. 2000;127:3457-3466.

    Not in our library10.1242/dev.127.16.3457

  32. 32.

    Kim J.E., Fei L., Yin W.C., Coquenlorge S., Rao-Bhatia A., Zhang X., Shi S.S.W., Lee J.H., Hahn N.A., Rizvi W. Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches. Nat. Commun. 2020;11:334.

    Not in our library10.1038/s41467-019-14058-5

  33. 33.
  34. 34.

    Kolterud A., Grosse A.S., Zacharias W.J., Walton K.D., Kretovich K.E., Madison B.B., Waghray M., Ferris J.E., Hu C., Merchant J.L. Paracrine Hedgehog signaling in stomach and intestine: new roles for hedgehog in gastrointestinal patterning. Gastroenterology. 2009;137:618-628.

    Not in our library10.1053/j.gastro.2009.05.002

  35. 35.

    Korinek V., Barker N., Moerer P., van Donselaar E., Huls G., Peters P.J., Clevers H. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat. Genet. 1998;19:379-383.

    Not in our library10.1038/1270

  36. 36.

    Kraiczy J., Nayak K., Ross A., Raine T., Mak T.N., Gasparetto M., Cario E., Rakyan V., Heuschkel R., Zilbauer M. Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease. Mucosal Immunol. 2016;9:647-658.

    Not in our library10.1038/mi.2015.88

  37. 37.
  38. 38.

    Kurahashi M., Niwa Y., Cheng J., Ohsaki Y., Fujita A., Goto H., Fujimoto T., Torihashi S. Platelet-derived growth factor signals play critical roles in differentiation of longitudinal smooth muscle cells in mouse embryonic gut. Neurogastroenterol. Motil. 2008;20:521-531.

    Not in our library10.1111/j.1365-2982.2007.01055.x

  39. 39.

    Li N., van Unen V., Abdelaal T., Guo N., Kasatskaya S.A., Ladell K., McLaren J.E., Egorov E.S., Izraelson M., Chuva de Sousa Lopes S.M. Memory CD4+ T cells are generated in the human fetal intestine. Nat. Immunol. 2019;20:301-312.

    Not in our library10.1038/s41590-018-0294-9

  40. 40.

    Lin C.C., Bradstreet T.R., Schwarzkopf E.A., Sim J., Carrero J.A., Chou C., Cook L.E., Egawa T., Taneja R., Murphy T.L. Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation. Nat. Commun. 2014;5:3551.

    Not in our library10.1038/ncomms4551

  41. 41.

    Lu X., Yu Y., Tan S. p53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis. BMC Gastroenterol. 2017;17:111.

    Not in our library10.1186/s12876-017-0665-y

  42. 42.

    Madison B.B., Braunstein K., Kuizon E., Portman K., Qiao X.T., Gumucio D.L. Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development. 2005;132:279-289.

    Not in our library10.1242/dev.01576

  43. 43.

    Mallow E.B., Harris A., Salzman N., Russell J.P., DeBerardinis R.J., Ruchelli E., Bevins C.L. Human enteric defensins. Gene structure and developmental expression. J. Biol. Chem. 1996;271:4038-4045.

    Not in our library10.1074/jbc.271.8.4038

  44. 44.

    Martin J.C., Chang C., Boschetti G., Ungaro R., Giri M., Grout J.A., Gettler K., Chuang L.S., Nayar S., Greenstein A.J. Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy. Cell. 2019;178:1493-1508.e20.

    Not in our library10.1016/j.cell.2019.08.008

  45. 45.

    McCarthy N., Manieri E., Storm E.E., Saadatpour A., Luoma A.M., Kapoor V.N., Madha S., Gaynor L.T., Cox C., Keerthivasan S. Distinct mesenchymal cell populations generate the essential intestinal BMP signaling gradient. Cell Stem Cell. 2020;26:391-402.e5.

    Not in our library10.1016/j.stem.2020.01.008

  46. 46.

    Moor A.E., Harnik Y., Ben-Moshe S., Massasa E.E., Rozenberg M., Eilam R., Bahar Halpern K., Itzkovitz S. Spatial reconstruction of single enterocytes uncovers broad zonation along the intestinal villus axis. Cell. 2018;175:1156-1167.e15.

    Not in our library10.1016/j.cell.2018.08.063

  47. 47.

    Muncan V., Heijmans J., Krasinski S.D., Büller N.V., Wildenberg M.E., Meisner S., Radonjic M., Stapleton K.A., Lamers W.H., Biemond I. Blimp1 regulates the transition of neonatal to adult intestinal epithelium. Nat. Commun. 2011;2:452.

    Not in our library10.1038/ncomms1463

  48. 48.

    Mustata R.C., Vasile G., Fernandez-Vallone V., Strollo S., Lefort A., Libert F., Monteyne D., Pérez-Morga D., Vassart G., Garcia M.I. Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium. Cell Rep. 2013;5:421-432.

    Not in our library10.1016/j.celrep.2013.09.005

  49. 49.

    Nowotschin S., Setty M., Kuo Y.Y., Liu V., Garg V., Sharma R., Simon C.S., Saiz N., Gardner R., Boutet S.C. The emergent landscape of the mouse gut endoderm at single-cell resolution. Nature. 2019;569:361-367.

    Not in our library10.1038/s41586-019-1127-1

  50. 50.
  51. 51.

    Parikh K., Antanaviciute A., Fawkner-Corbett D., Jagielowicz M., Aulicino A., Lagerholm C., Davis S., Kinchen J., Chen H.H., Alham N.K. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature. 2019;567:49-55.

    Not in our library10.1038/s41586-019-0992-y

  52. 52.

    Pedregosa F., Varoquaux G., Gramfort A., Michel V., Thirion B., Grisel O., Blondel M., Müller A., Nothman J., Louppe G. Scikit-learn machine learning in Python. J. Mach. Learn. Res. 2011;12:2825-2830.

    Not in our library

  53. 53.
  54. 54.

    Rao-Bhatia A., Zhu M., Yin W.C., Coquenlorge S., Zhang X., Woo J., Sun Y., Dean C.H., Liu A., Hui C.-C. Hedgehog-activated Fat4 and PCP pathways mediate mesenchymal cell clustering and villus formation in gut development. Dev. Cell. 2020;52:647-658.e6.

    Not in our library10.1016/j.devcel.2020.02.003

  55. 55.

    Sato T., Stange D.E., Ferrante M., Vries R.G., Van Es J.H., Van den Brink S., Van Houdt W.J., Pronk A., Van Gorp J., Siersema P.D., Clevers H. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology. 2011;141:1762-1772.

    Not in our library10.1053/j.gastro.2011.07.050

  56. 56.

    Sato T., van Es J.H., Snippert H.J., Stange D.E., Vries R.G., van den Born M., Barker N., Shroyer N.F., van de Wetering M., Clevers H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469:415-418.

    Not in our library10.1038/nature09637

  57. 57.

    Schreurs R.R.C.E., Baumdick M.E., Sagebiel A.F., Kaufmann M., Mokry M., Klarenbeek P.L., Schaltenberg N., Steinert F.L., van Rijn J.M., Drewniak A. Human fetal TNF-α-cytokine-producing CD4+ effector memory T cells promote intestinal development and mediate inflammation early in life. Immunity. 2019;50:462-476.e8.

    Not in our library10.1016/j.immuni.2018.12.010

  58. 58.

    Scialdone A., Natarajan K.N., Saraiva L.R., Proserpio V., Teichmann S.A., Stegle O., Marioni J.C., Buettner F. Computational assignment of cell-cycle stage from single-cell transcriptome data. Methods. 2015;85:54-61.

    Not in our library10.1016/j.ymeth.2015.06.021

  59. 59.

    Shoshkes-Carmel M., Wang Y.J., Wangensteen K.J., Tóth B., Kondo A., Massasa E.E., Itzkovitz S., Kaestner K.H. Author Correction: subepithelial telocytes are an important source of Wnts that supports intestinal crypts. Nature. 2018;560:E29.

    Not in our library10.1038/s41586-018-0286-9

  60. 60.

    Shyer A.E., Huycke T.R., Lee C., Mahadevan L., Tabin C.J. Bending gradients: how the intestinal stem cell gets its home. Cell. 2015;161:569-580.

    Not in our library10.1016/j.cell.2015.03.041

  61. 61.

    Shyer A.E., Tallinen T., Nerurkar N.L., Wei Z., Gil E.S., Kaplan D.L., Tabin C.J., Mahadevan L. Villification: how the gut gets its villi. Science. 2013;342:212-218.

    Not in our library10.1126/science.1238842

  62. 62.

    Smillie C.S., Biton M., Ordovas-Montanes J., Sullivan K.M., Burgin G., Graham D.B., Herbst R.H., Rogel N., Slyper M., Waldman J. Intra- and inter-cellular rewiring of the human colon during ulcerative colitis. Cell. 2019;178:714-730.e22.

    Not in our library10.1016/j.cell.2019.06.029

  63. 63.

    Sonntag B., Stolze B., Heinecke A., Luegering A., Heidemann J., Lebiedz P., Rijcken E., Kiesel L., Domschke W., Kucharzik T., Maaser C. Preterm birth but not mode of delivery is associated with an increased risk of developing inflammatory bowel disease later in life. Inflam. Bowel Dis. 2007;13:1385-1390.

    Not in our library10.1002/ibd.20206

  64. 64.

    Spence J.R., Lauf R., Shroyer N.F. Vertebrate intestinal endoderm development. Dev. Dyn. 2011;240:501-520.

    Not in our library10.1002/dvdy.22540

  65. 65.

    Strimmer K. fdrtool: a versatile R package for estimating local and tail area-based false discovery rates. Bioinformatics. 2008;24:1461-1462.

    Not in our library10.1093/bioinformatics/btn209

  66. 66.

    Svensson V., Pachter L. RNA velocity: molecular kinetics from single-cell RNA-seq. Mol. Cell. 2018;72:7-9.

    Not in our library10.1016/j.molcel.2018.09.026

  67. 67.

    Takaishi H., Kanai T., Nakazawa A., Sugata F., Nikai A., Yoshizawa S., Hamamoto Y., Funakoshi S., Yajima T., Iwao Y. Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies (ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype. J. Gastroenterol. 2012;47:969-977.

    Not in our library10.1007/s00535-012-0566-3

  68. 68.

    Teng Y.-S., Zhao Y.-L., Li M.-S., Liu Y.-G., Cheng P., Lv Y.-P., Mao F.-Y., Chen W., Yang S.-M., Hao C.-J. Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p-STAT3 in Helicobacter pylori-associated gastritis. FASEB J. 2020;34:1169-1181.

    Not in our library10.1096/fj.201900464rr

  69. 69.
  70. 70.

    Tsai Y.H., Nattiv R., Dedhia P.H., Nagy M.S., Chin A.M., Thomson M., Klein O.D., Spence J.R. In vitro patterning of pluripotent stem cell-derived intestine recapitulates in vivo human development. Development. 2017;144:1045-1055.

    Not in our library10.1242/dev.138453

  71. 71.

    Vento-Tormo R., Efremova M., Botting R.A., Turco M.Y., Vento-Tormo M., Meyer K.B., Park J.E., Stephenson E., Polański K., Goncalves A. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature. 2018;563:347-353.

    Not in our library10.1038/s41586-018-0698-6

  72. 72.

    Vitali R., Stronati L., Negroni A., Di Nardo G., Pierdomenico M., del Giudice E., Rossi P., Cucchiara S. Fecal HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel disease. Am. J. Gastroenterol. 2011;106:2029-2040.

    Not in our library10.1038/ajg.2011.231

  73. 73.

    Walton K.D., Kolterud A., Czerwinski M.J., Bell M.J., Prakash A., Kushwaha J., Grosse A.S., Schnell S., Gumucio D.L. Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi. Proc. Natl. Acad. Sci. USA. 2012;109:15817-15822.

    Not in our library10.1073/pnas.1205669109

  74. 74.

    Walton K.D., Freddo A.M., Wang S., Gumucio D.L. Generation of intestinal surface: an absorbing tale. Development. 2016;143:2261-2272.

    Not in our library10.1242/dev.135400

  75. 75.

    Walton K.D., Whidden M., Kolterud Å., Shoffner S.K., Czerwinski M.J., Kushwaha J., Parmar N., Chandhrasekhar D., Freddo A.M., Schnell S., Gumucio D.L. Villification in the mouse: Bmp signals control intestinal villus patterning. Development. 2016;143:427-436.

    Not in our library10.1242/dev.130112

  76. 76.
  77. 77.

    Wehkamp J., Wang G., Kübler I., Nuding S., Gregorieff A., Schnabel A., Kays R.J., Fellermann K., Burk O., Schwab M. The Paneth Cell α-Defensin Deficiency of Ileal Crohn’s disease Is Linked to Wnt/Tcf-4. J. Immunol. 2007;179:3109-3118.

    Not in our library10.4049/jimmunol.179.5.3109

  78. 78.
  79. 79.
  80. 80.

    Wolock S.L., Lopez R., Klein A.M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 2019;8:281-291.e9.

    Not in our library10.1016/j.cels.2018.11.005

  81. 81.

    Wu Y., Kimura Y., Okamoto T., Matsuhisa K., Asada R., Saito A., Sakaue F., Imaizumi K., Kaneko M. Inflammatory bowel disease-associated ubiquitin ligase RNF183 promotes lysosomal degradation of DR5 and TRAIL-induced caspase activation. Sci. Rep. 2019;9:20301.

    Not in our library10.1038/s41598-019-56748-6

  82. 82.

    Xian L., Georgess D., Huso T., Cope L., Belton A., Chang Y.T., Kuang W., Gu Q., Zhang X., Senger S. HMGA1 amplifies Wnt signalling and expands the intestinal stem cell compartment and Paneth cell niche. Nat. Commun. 2017;8:15008.

    Not in our library10.1038/ncomms15008

  83. 83.

    Yanai H., Atsumi N., Tanaka T., Nakamura N., Komai Y., Omachi T., Tanaka K., Ishigaki K., Saiga K., Ohsugi H. Intestinal stem cells contribute to the maturation of the neonatal small intestine and colon independently of digestive activity. Sci. Rep. 2017;7:9891.

    Not in our library10.1038/s41598-017-09927-2

  84. 84.

    Ye H., Kelly T.F., Samadani U., Lim L., Rubio S., Overdier D.G., Roebuck K.A., Costa R.H. Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues. Mol. Cell. Biol. 1997;17:1626-1641.

    Not in our library10.1128/mcb.17.3.1626

  85. 85.

    Yu F., Sharma S., Jankovic D., Gurram R.K., Su P., Hu G., Li R., Rieder S., Zhao K., Sun B., Zhu J. The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination. J. Exp. Med. 2018;215:1813-1821.

    Not in our library10.1084/jem.20170155

  86. 86.

    Yu Q., Kilik U., Holloway E.M., Tsai Y.-H., Wu A., Wu J.H., Czerwinski M., Childs C., He Z., Glass I.A. An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine bioRxiv. 2020.

    Not in our library10.1101/2020.07.24.219147

  87. 87.

    Yui S., Azzolin L., Maimets M., Pedersen M.T., Fordham R.P., Hansen S.L., Larsen H.L., Guiu J., Alves M.R.P., Rundsten C.F. YAP/TAZ-dependent reprogramming 7of colonic epithelium links ECM remodeling to tissue regeneration. Cell Stem Cell. 2018;22:35-49.e7.

    Not in our library10.1016/j.stem.2017.11.001

  88. 88.
  89. 89.

Cited by papers we hold 8

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.