2023
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetSOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced Metaplasia
Willet S, Thanintorn N, McNeill H, Huh S, Ornitz D, Huh W, Hoft S, DiPaolo R, Mills J. SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced Metaplasia. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 325-339. PMID: 37270061, PMCID: PMC10444955, DOI: 10.1016/j.jcmgh.2023.05.009.Peer-Reviewed Original ResearchConceptsSRY-box transcription factor 9Cell identityAdult homeostasisGastric progenitorsMucous neck cellsZymogenic chief cellsGastric developmentNeck cellsPotential genesMaster regulatorExpression patternsGene expressionSPEM cellsCell differentiationCorpus unitsSOX9 expressionSOX9Factor 9Specific expansionHomeostasisMisexpressionSox9 deletionReprogrammingChief cellsGenetic deletion
2021
Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps
Chen B, Scurrah CR, McKinley ET, Simmons AJ, Ramirez-Solano MA, Zhu X, Markham NO, Heiser CN, Vega PN, Rolong A, Kim H, Sheng Q, Drewes JL, Zhou Y, Southard-Smith AN, Xu Y, Ro J, Jones AL, Revetta F, Berry LD, Niitsu H, Islam M, Pelka K, Hofree M, Chen JH, Sarkizova S, Ng K, Giannakis M, Boland GM, Aguirre AJ, Anderson AC, Rozenblatt-Rosen O, Regev A, Hacohen N, Kawasaki K, Sato T, Goettel JA, Grady WM, Zheng W, Washington MK, Cai Q, Sears CL, Goldenring JR, Franklin JL, Su T, Huh WJ, Vandekar S, Roland JT, Liu Q, Coffey RJ, Shrubsole MJ, Lau KS. Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps. Cell 2021, 184: 6262-6280.e26. PMID: 34910928, PMCID: PMC8941949, DOI: 10.1016/j.cell.2021.11.031.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdenomaAdultAgedAnimalsCarcinogenesisCell DeathCell DifferentiationColonic PolypsColorectal NeoplasmsDisease ProgressionFemaleGene Expression Regulation, NeoplasticGene Regulatory NetworksGenetic HeterogeneityHumansMaleMiceMiddle AgedMutationNeoplastic Stem CellsReproducibility of ResultsRNA-SeqSingle-Cell AnalysisTumor MicroenvironmentConceptsHuman colorectal polypsColorectal cancerColorectal polypsPrevention of CRCMicrosatellite-unstable colorectal cancersUnstable colorectal cancersGastric metaplasiaImmune microenvironmentTumor cell differentiation statusImmune cellsPrecision surveillancePrecursor polypsSerrated polypsConventional adenomasStem cell propertiesMalignant progressionImmunogenic potentialPolypsTumor cellsTherapeutic insightsCell differentiation statusCellular originMetaplasiaAdenomasMolecular heterogeneityCell-Autonomous Role of EGFR in Spontaneous Duodenal Tumors in LRIG1 Null Mice
Niitsu H, Lu Y, Huh W, Love A, Franklin J, Coffey R. Cell-Autonomous Role of EGFR in Spontaneous Duodenal Tumors in LRIG1 Null Mice. Cellular And Molecular Gastroenterology And Hepatology 2021, 12: 1159-1162.e4. PMID: 33989815, PMCID: PMC8413138, DOI: 10.1016/j.jcmgh.2021.05.004.Peer-Reviewed Original Research
2020
A smooth muscle‐derived, Braf‐driven mouse model of gastrointestinal stromal tumor (GIST): evidence for an alternative GIST cell‐of‐origin
Kondo J, Huh WJ, Franklin JL, Heinrich MC, Rubin BP, Coffey RJ. A smooth muscle‐derived, Braf‐driven mouse model of gastrointestinal stromal tumor (GIST): evidence for an alternative GIST cell‐of‐origin. The Journal Of Pathology 2020, 252: 441-450. PMID: 32944951, PMCID: PMC7802691, DOI: 10.1002/path.5552.Peer-Reviewed Original ResearchConceptsGastrointestinal stromal tumorsSmooth muscle cellsICC hyperplasiaMuscle cellsTyrosine kinase inhibitor imatinibFrequent driver eventsCommon mesenchymal tumorsSmooth muscle cell progenitorsDevelopment of GISTsKinase inhibitor imatinibLoss of Trp53ICC-DMPGut motilityStromal tumorsMesenchymal tumorsMouse modelInhibitor imatinibInterstitial cellsMutant BRAFBRAF expressionTumorsBRAFHyperplasiaCell progenitorsDriver eventsNoggin regulates foregut progenitor cell programming and mis-expression leads to esophageal atresia
Pinzon-Guzman C, Sangadala S, Riera KM, Popova EY, Manning E, Huh WJ, Alexander MS, Shelton JS, Boden SD, Goldenring JR. Noggin regulates foregut progenitor cell programming and mis-expression leads to esophageal atresia. Journal Of Clinical Investigation 2020, 130: 4396-4410. PMID: 32427591, PMCID: PMC7410075, DOI: 10.1172/jci123597.Peer-Reviewed Original Research
2019
Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress
Byrd KM, Piehl NC, Patel JH, Huh WJ, Sequeira I, Lough KJ, Wagner BL, Marangoni P, Watt FM, Klein OD, Coffey RJ, Williams SE. Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress. Cell Stem Cell 2019, 25: 814-829.e6. PMID: 31809739, PMCID: PMC6925542, DOI: 10.1016/j.stem.2019.11.005.Peer-Reviewed Original ResearchConceptsStem cell populationJunctional zoneOral mucosaStem cellsImportant model systemCell populationsEpithelial stem cell populationSingle-progenitor modelAsymmetric divisionLabel-retention assaysCandidate nichesSymmetric divisionTissue stressOral cavityPalatal epitheliumPhysiological stressModel systemStratified epitheliumMucosaProliferative heterogeneityEpithelium
2017
A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo
Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJ. A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo. Cell Reports 2017, 19: 1257-1267. PMID: 28494873, PMCID: PMC5517093, DOI: 10.1016/j.celrep.2017.04.048.Peer-Reviewed Original ResearchConceptsEGF receptorEGFR localizationEndogenous regulatory elementsDistinct cell populationsReporter miceGenome editingEGFR internalizationRegulatory elementsCRISPR/C-terminusEndogenous EGFRFluorescent reportersDifferentiated compartmentVillus compartmentTraffickingCell populationsReporterExpressionEGFR expressionDisease statesDistinct patternsCompartmentsAdjacent epitheliumIntestinal tumorsAdult mice
2016
Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium
Moore BD, Khurana SS, Huh WJ, Mills JC. Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium. AJP Gastrointestinal And Liver Physiology 2016, 311: g267-g275. PMID: 27340127, PMCID: PMC5007292, DOI: 10.1152/ajpgi.00195.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsBinding SitesCell DifferentiationCell LineCell ProliferationEpithelial CellsGastric MucosaGene Expression RegulationGenotypeHepatocyte Nuclear Factor 4HomeostasisHumansMice, KnockoutPhenotypePromoter Regions, GeneticSignal TransductionTransfectionX-Box Binding Protein 1ConceptsZymogenic chief cellsAdult mouse stomachX-box binding protein 1Gastric unitsRole of HNF4αStem cell zoneHepatocyte nuclear factor 4 alphaLoss of HNF4αBinding protein 1Nuclear factor 4 alphaHepatocyte nuclear factor 4αHuman gastric cancer cellsMouse stomachTranscriptional regulatorsChromatin immunoprecipitationNuclear factor 4αGastric cancer cellsXBP1 mRNAHNF4α proteinTranscription factorsUpstream regulationMouse gastric epitheliumHuman gastric cellsCell differentiationAdditional phenotypes
2013
Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3
Geahlen JH, Lapid C, Thorell K, Nikolskiy I, Huh WJ, Oates EL, Lennerz JK, Tian X, Weis VG, Khurana SS, Lundin SB, Templeton AR, Mills JC. Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3. Physiological Genomics 2013, 45: 667-683. PMID: 23715263, PMCID: PMC3742967, DOI: 10.1152/physiolgenomics.00169.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsComputational BiologyDNA PrimersEvolution, MolecularFluorescent Antibody TechniqueGastric MucosaGenetic LociGenetics, PopulationGenotypeHaplotypesHumansLikelihood FunctionsMacaca mulattaMembrane ProteinsMiceMice, Inbred C57BLMicroarray AnalysisMicroscopy, ConfocalModels, GeneticMutationPhylogenyPolymorphism, Single NucleotidePseudogenesRacial GroupsSelection, GeneticSpecies SpecificitySus scrofaConceptsSelective sweepsHuman genetic locusGenome evolutionGenomic neighborsSplice donor siteDirectional selectionHuman genomeGenetic lociBp downstreamEuropean genesGKN3Gastric mucous neck cellsStop codon mutationThird memberHuman populationGenesCodon mutationLociGKN2Haplotype analysisMucous neck cellsMutationsAfrican populationsNeck cellsGKN1
2011
Tamoxifen Induces Rapid, Reversible Atrophy, and Metaplasia in Mouse Stomach
Huh WJ, Khurana SS, Geahlen JH, Kohli K, Waller RA, Mills JC. Tamoxifen Induces Rapid, Reversible Atrophy, and Metaplasia in Mouse Stomach. Gastroenterology 2011, 142: 21-24.e7. PMID: 22001866, PMCID: PMC3708546, DOI: 10.1053/j.gastro.2011.09.050.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsAtrophyChief Cells, GastricFemaleGene Expression RegulationInjections, IntraperitonealIntegrasesLac OperonMaleMetaplasiaMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicParietal Cells, GastricSelective Estrogen Receptor ModulatorsSpecies SpecificityTamoxifenTime FactorsConceptsSelective estrogen receptor modulatorsParietal cellsBody weight doseEstrogen receptor modulatorsTamoxifen side effectsAcid secretion inhibitionZymogenic chief cellsReversible atrophyWeight doseGastric toxicityIntraperitoneal administrationReceptor modulatorsNormal miceSide effectsSecretion inhibitionGastric parietal cellsChief cellsMouse stomachTamoxifenMetaplasiaMultiple strainsToxicityCellsPatientsAtrophy
2010
XBP1 Controls Maturation of Gastric Zymogenic Cells by Induction of MIST1 and Expansion of the Rough Endoplasmic Reticulum
Huh WJ, Esen E, Geahlen JH, Bredemeyer AJ, Lee A, Shi G, Konieczny SF, Glimcher LH, Mills JC. XBP1 Controls Maturation of Gastric Zymogenic Cells by Induction of MIST1 and Expansion of the Rough Endoplasmic Reticulum. Gastroenterology 2010, 139: 2038-2049. PMID: 20816838, PMCID: PMC2997137, DOI: 10.1053/j.gastro.2010.08.050.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsCell DifferentiationCell LineChief Cells, GastricDNA-Binding ProteinsEndoplasmic Reticulum, RoughIntegrasesMiceMice, KnockoutMicroscopy, Electron, TransmissionPromoter Regions, GeneticRegulatory Factor X Transcription FactorsSecretory VesiclesStem CellsTranscription FactorsX-Box Binding Protein 1ConceptsEndoplasmic reticulumZymogenic cellsRough endoplasmic reticulumNC markersGastric zymogenic cellsTranscription factor XBP1Large secretory vesiclesLamellar rough endoplasmic reticulumAbsence of XBP1Transcription factor MIST1Cell shape abnormalitiesCre-loxP systemTranscriptional regulationChromatin immunoprecipitationTranscriptional activationSecretory vesiclesGastric cell linesMist1Neck cellsXBP1Cell typesImmunoblot analysisCell linesQuantitative reverse transcriptase-polymerase chain reactionMIST1 expressionInducible activation of Cre recombinase in adult mice causes gastric epithelial atrophy, metaplasia, and regenerative changes in the absence of “floxed” alleles
Huh WJ, Mysorekar IU, Mills JC. Inducible activation of Cre recombinase in adult mice causes gastric epithelial atrophy, metaplasia, and regenerative changes in the absence of “floxed” alleles. AJP Gastrointestinal And Liver Physiology 2010, 299: g368-g380. PMID: 20413717, PMCID: PMC3774481, DOI: 10.1152/ajpgi.00021.2010.Peer-Reviewed Original ResearchConceptsInduction of CreGastric epithelial stem cellsSpasmolytic polypeptide-expressing metaplasiaFoci of hyperplasiaSubset of miceTdT-mediated dUTP nick end labelingRegenerative capacityDUTP nick end labelingNick end labelingStem cellsAntral polypsDNA damage markerChicken actin promoterEpithelial atrophyStandard dosesGastric bodyPositive apoptosisEpithelial stem cellsComplete healingProfound atrophyGastric mucosaDamage markersAdult miceLoxP-flanked allelesSevere injuries
2008
The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage
Bredemeyer AJ, Geahlen JH, Weis VG, Huh WJ, Zinselmeyer BH, Srivatsan S, Miller MJ, Shaw AS, Mills JC. The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage. Developmental Biology 2008, 325: 211-224. PMID: 19013146, PMCID: PMC2634829, DOI: 10.1016/j.ydbio.2008.10.025.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBasic Helix-Loop-Helix Transcription FactorsCadherinsCell DifferentiationCell LineageCell PolarityCell ProliferationChief Cells, GastricCytoskeletal ProteinsEpithelial CellsIntercellular JunctionsMiceModels, BiologicalParietal Cells, GastricProtein BindingProtein TransportStem Cell NicheStem CellsConceptsZymogenic cellsProgenitor nicheCell fate decisionsE-cadherin localizationZymogenic cell lineagesMammalian gastrointestinal tractProgenitor cell nicheParietal cellsLineage progenitor cellsKey cellular componentsFate decisionsDiverse lineagesProgenitor stateDifferentiated cell markersCell nicheGastric parietal cellsCell lineagesPremature expressionCellular componentsGastric unitsLineagesNicheGenetic ablationLineage cellsProgenitor cells
2006
Location, allocation, relocation: isolating adult tissue stem cells in three dimensions
Huh WJ, Pan XO, Mysorekar IU, Mills JC. Location, allocation, relocation: isolating adult tissue stem cells in three dimensions. Current Opinion In Biotechnology 2006, 17: 511-517. PMID: 16889955, DOI: 10.1016/j.copbio.2006.07.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements