2020
Pumilio proteins utilize distinct regulatory mechanisms to achieve complementary functions required for pluripotency and embryogenesis
Uyhazi KE, Yang Y, Liu N, Qi H, Huang XA, Mak W, Weatherbee SD, de Prisco N, Gennarino VA, Song X, Lin H. Pumilio proteins utilize distinct regulatory mechanisms to achieve complementary functions required for pluripotency and embryogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7851-7862. PMID: 32198202, PMCID: PMC7148564, DOI: 10.1073/pnas.1916471117.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsTarget messenger RNAsPumilio proteinsPUM proteinsMessenger RNAEssential functionsStem cell maintenanceDistinct regulatory mechanismsEmbryonic day 8.5ESC pluripotencyTranslational regulatorPluripotency genesGene regulationEarly embryogenesisDifferentiation genesPosttranscriptional levelHigh homologyMRNA stabilityRegulatory mechanismsDouble mutant micePluripotencyDay 8.5Morula stagePluripotency markersEmbryogenesis
2017
Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins
Zhang M, Chen D, Xia J, Han W, Cui X, Neuenkirchen N, Hermes G, Sestan N, Lin H. Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins. Genes & Development 2017, 31: 1354-1369. PMID: 28794184, PMCID: PMC5580656, DOI: 10.1101/gad.298752.117.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCytoplasmDentate GyrusFemaleFragile X Mental Retardation ProteinGene Expression Regulation, DevelopmentalGene Knockout TechniquesGene SilencingLearning DisabilitiesMaleMemory DisordersMiceNeural Stem CellsNeurogenesisNeuronsRNA, MessengerRNA-Binding ProteinsStem CellsConceptsPost-transcriptional regulationPost-transcriptional regulatorsNeural stem cellsTarget mRNAsMost target mRNAsRNA-dependent interactionCross-linking immunoprecipitationThousands of mRNAsMental retardation proteinPUM proteinsPumilio proteinsPumilio 1Mouse neurogenesisMammalian neurogenesisPerinatal apoptosisPUM1PUM2Stem cellsProteinCommon targetMRNARegulatorNeurogenesisCell compositionRegulation
2015
Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis
Gonzalez J, Qi H, Liu N, Lin H. Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis. Cell Reports 2015, 12: 150-161. PMID: 26119740, PMCID: PMC4497877, DOI: 10.1016/j.celrep.2015.06.004.Peer-Reviewed Original ResearchConceptsGermline stem cellsDrosophila testisSomatic cyst cellsPIWI-piRNA pathwayStem cell maintenanceCell-autonomous functionStem cellsGerm cell differentiationStem cell typesFasciclin 3GSC daughtersGermline functionSomatic rolePiwi expressionCyst cellsCell maintenanceEpigenetic mechanismsPiwiGenes keyNuclear localizationKey regulatorMolecular mechanismsCell differentiationGonadal developmentCell types
2014
PIWI Proteins Are Dispensable for Mouse Somatic Development and Reprogramming of Fibroblasts into Pluripotent Stem Cells
Cheng EC, Kang D, Wang Z, Lin H. PIWI Proteins Are Dispensable for Mouse Somatic Development and Reprogramming of Fibroblasts into Pluripotent Stem Cells. PLOS ONE 2014, 9: e97821. PMID: 25238487, PMCID: PMC4169525, DOI: 10.1371/journal.pone.0097821.Peer-Reviewed Original ResearchConceptsPIWI proteinsEmbryonic stem cellsInduced pluripotent stem cellsPluripotent stem cellsIPS cellsPiwi genesGermline stem cell maintenanceStem cellsControl iPS cellsDifferentiated somatic cellsStem cell maintenancePIWI protein familyReprogramming of fibroblastsExpression profiling revealsGermline developmentProtein familyKnockout embryosCell maintenanceFemale fertileSomatic cellsEmbryonic fibroblastsDirect reprogrammingProfiling revealsTeratoma assayGerm layersPiwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary
Ma X, Wang S, Do T, Song X, Inaba M, Nishimoto Y, Liu LP, Gao Y, Mao Y, Li H, McDowell W, Park J, Malanowski K, Peak A, Perera A, Li H, Gaudenz K, Haug J, Yamashita Y, Lin H, Ni JQ, Xie T. Piwi Is Required in Multiple Cell Types to Control Germline Stem Cell Lineage Development in the Drosophila Ovary. PLOS ONE 2014, 9: e90267. PMID: 24658126, PMCID: PMC3962343, DOI: 10.1371/journal.pone.0090267.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsCell DifferentiationCell LineageDNA DamageDrosophilaDrosophila ProteinsFemaleOvarySignal TransductionConceptsGerm cell differentiationDrosophila ovaryGermline stem cellsSomatic cellsCell differentiationGerm cellsPiRNA productionMultiple cell typesGSC maintenanceTransposable elementsGerm lineLineage developmentCell typesPiRNA pathway componentsGerm cell maintenanceCell lineage developmentUndifferentiated germ cellsCell-specific knockdownEscort cellsGSC establishmentGSC lossPiwi knockdownPiRNA pathwayGenome stabilityTE transcripts
2013
PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells
Juliano CE, Reich A, Liu N, Götzfried J, Zhong M, Uman S, Reenan RA, Wessel GM, Steele RE, Lin H. PIWI proteins and PIWI-interacting RNAs function in Hydra somatic stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 111: 337-342. PMID: 24367095, PMCID: PMC3890812, DOI: 10.1073/pnas.1320965111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsCell DifferentiationCell LineageCell SeparationCytoplasmEpithelial CellsFlow CytometryGene Expression RegulationHydraPhylogenyRecombinant ProteinsRNARNA InterferenceRNA Processing, Post-TranscriptionalRNA, Small InterferingSpecies SpecificityStem CellsTranscriptomeTransgenesConceptsPIWI-interacting RNAsPIWI proteinsStem/progenitor cellsProgenitor cellsPIWI-piRNA pathwayPing-pong signatureSomatic stem/progenitor cellsStem cell functionalitySomatic stem cellsInterstitial lineageNonbilaterian animalsPiwi functionPiRNA biogenesisAnimal germlineTransposon transcriptsSimple metazoanCnidarian HydraSmall RNAsEndodermal lineagesRNA functionPosttranscriptional regulatorsEpithelial lineageLineagesLikely actsPiwi
2011
The microRNA regulation of stem cells.
Huang X, Lin H. The microRNA regulation of stem cells. WIREs Mechanisms Of Disease 2011, 1: 83-95. PMID: 23801669, DOI: 10.1002/wdev.5.Peer-Reviewed Original Research
2010
High-efficiency siRNA-based gene knockdown in human embryonic stem cells
Ma Y, Jin J, Dong C, Cheng EC, Lin H, Huang Y, Qiu C. High-efficiency siRNA-based gene knockdown in human embryonic stem cells. RNA 2010, 16: 2564-2569. PMID: 20978109, PMCID: PMC2995416, DOI: 10.1261/rna.2350710.Peer-Reviewed Original ResearchDynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing
Wu JQ, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S, Raha D, Egholm M, Lin H, Weissman S, Cui W, Gerstein M, Snyder M. Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 5254-5259. PMID: 20194744, PMCID: PMC2841935, DOI: 10.1073/pnas.0914114107.Peer-Reviewed Original ResearchConceptsNeural differentiationUndifferentiated hESCsNeural fate specificationCell identity maintenanceStage-specific regulationHuman embryonic stem cellsTypes of genesPaired-end sequencingDifferentiation of hESCsEmbryonic stem cellsPaired-end readsNeural cell differentiationSplicing dynamicsFate specificationDynamic transcriptomeIsoform diversityTranscriptome changesUnannotated transcriptsGene transcriptionRNA sequencingStages of differentiationNeural lineagesCell differentiationDifferential expressionGliogenic potential
2009
MicroRNAs: key regulators of stem cells
Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nature Reviews Molecular Cell Biology 2009, 10: 116-125. PMID: 19165214, PMCID: PMC4118578, DOI: 10.1038/nrm2621.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsAdult tissue stem cellsStem cell processesTissue stem cellsSmall RNAsStem cellsCell processesNext-generation sequencing technologiesKey protein factorsLong non-coding RNAsNon-coding RNAsNumber of miRNAsGeneration sequencing technologyTranscriptional machineryNew miRNAsAsymmetric divisionDaughter cellsTarget mRNAsProtein factorsMaster regulatorSequencing technologiesKey regulatorUntranslated regionDifferentiation pathwayMiRNAs
2008
MILI, a PIWI-interacting RNA-binding Protein, Is Required for Germ Line Stem Cell Self-renewal and Appears to Positively Regulate Translation*
Unhavaithaya Y, Hao Y, Beyret E, Yin H, Kuramochi-Miyagawa S, Nakano T, Lin H. MILI, a PIWI-interacting RNA-binding Protein, Is Required for Germ Line Stem Cell Self-renewal and Appears to Positively Regulate Translation*. Journal Of Biological Chemistry 2008, 284: 6507-6519. PMID: 19114715, PMCID: PMC2649106, DOI: 10.1074/jbc.m809104200.Peer-Reviewed Original ResearchConceptsGerm line stem cellsStem cellsArgonaute/PIWI protein familyMicro-RNA pathwayGerm line developmentMammalian stem cellsPIWI-interacting RNAsCap-binding complexRNA-binding proteinPIWI protein familyCellular mRNA levelsStem cell populationSelf-renewing divisionsArgonaute functionsPIWI proteinsRegulates TranslationPIWI subfamiliesEpigenetic regulationProtein familyCell maintenanceRNA interferenceChromatoid bodyMILIMolecular mechanismsEarly spermatocytesCell biology of stem cells: an enigma of asymmetry and self-renewal
Lin H. Cell biology of stem cells: an enigma of asymmetry and self-renewal. Journal Of Cell Biology 2008, 180: 257-260. PMID: 18227277, PMCID: PMC2213586, DOI: 10.1083/jcb.200712159.Peer-Reviewed Original ResearchConceptsCell biologyStem cellsIntrinsic cell polarityDrosophila melanogaster neuroblastsGermline stem cellsStem cell divisionStem cell systemCell cycle regulatorsSkin stem cellsNiche signalingCell polarityAsymmetric divisionDaughter cellsCell divisionCycle regulatorsStem cell researchBiologyCell researchCell systemCellsCrucial roleTherapeutic applicationsDivisionDiverse typesCentrosomes
2007
Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation
Chen L, Shen R, Ye Y, Pu XA, Liu X, Duan W, Wen J, Zimmerer J, Wang Y, Liu Y, Lasky LC, Heerema NA, Perrotti D, Ozato K, Kuramochi-Miyagawa S, Nakano T, Yates AJ, Carson WE, Lin H, Barsky SH, Gao JX. Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation. PLOS ONE 2007, 2: e293. PMID: 17356702, PMCID: PMC1808425, DOI: 10.1371/journal.pone.0000293.Peer-Reviewed Original ResearchConceptsCancer stem cellsMalignant differentiationPrecancerous stem cellsStem cellsImmunocompetent miceImmunodeficient miceSolid cancersSolid tumorsTherapy of cancerC-kitNovel targetCancerEarly detectionCancer cellsSca-1Lineage markersTissue cellsMicePCSCsCellsSingle cloneDifferentiationTherapyTumorsPrevention
2006
Sex-lethal is a target of Bruno-mediated translational repression in promoting the differentiation of stem cell progeny during Drosophila oogenesis
Wang Z, Lin H. Sex-lethal is a target of Bruno-mediated translational repression in promoting the differentiation of stem cell progeny during Drosophila oogenesis. Developmental Biology 2006, 302: 160-168. PMID: 17067567, PMCID: PMC1904479, DOI: 10.1016/j.ydbio.2006.09.016.Peer-Reviewed Original ResearchConceptsBruno response elementCystoblast differentiationTranslational repressionElectrophoresis mobility shift assaysGermline stem cellsPotential mRNA targetsMobility shift assaysStem cell progenySex-lethalDrosophila ovaryDrosophila oogenesisMutant phenotypeBioinformatics approachMRNA targetsShift assaysType RNACDNA constructsUntranslated regionCell progenyResponse elementStem cellsNovel targetDifferentiationRepressionMS11The Role of PIWI and the miRNA Machinery in Drosophila Germline Determination
Megosh HB, Cox DN, Campbell C, Lin H. The Role of PIWI and the miRNA Machinery in Drosophila Germline Determination. Current Biology 2006, 16: 1884-1894. PMID: 16949822, DOI: 10.1016/j.cub.2006.08.051.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsBody PatterningCell DifferentiationDEAD-box RNA HelicasesDrosophilaDrosophila ProteinsEmbryo, NonmammalianEmbryonic DevelopmentFragile X Mental Retardation ProteinGene Expression Regulation, DevelopmentalGerm CellsMicroRNAsProteinsRibonuclease IIIRNA HelicasesRNA, Small InterferingRNA-Induced Silencing ComplexConceptsGermline determinationDicer-1Dicer-2MiRNA pathwayRole of PiwiReduced PGC numbersNumber of PGCsMiRISC complexesRasiRNA pathwayGermline specificationDrosophila PiwiSiRNA pathwayAbdominal patterningVasa expressionTranslational regulationPGC numberPiwiMiRNA machineryGerm plasmMolecular activityPolar granuleDFMRPCell formationOSKMaternal component
2005
Regulatory Relationship among piwi, pumilio, and bag-of-marbles in Drosophila Germline Stem Cell Self-Renewal and Differentiation
Szakmary A, Cox DN, Wang Z, Lin H. Regulatory Relationship among piwi, pumilio, and bag-of-marbles in Drosophila Germline Stem Cell Self-Renewal and Differentiation. Current Biology 2005, 15: 171-178. PMID: 15668175, DOI: 10.1016/j.cub.2005.01.005.Peer-Reviewed Original ResearchConceptsGermline stem cellsPiwi functionDrosophila ovarian germline stem cellsOvarian germline stem cellsStem Cell Self-RenewalFunction of PiwiDifferentiated daughter cellsCell Self-RenewalGerm cell divisionBam proteinCystoblast differentiationBam expressionMutant ovariesNiche signalsDouble mutantDaughter cellsDifferentiation genesPiwiCell divisionNiche cellsRegulatory relationshipsSelf-RenewalGerm cellsMutantsCystoblasts
2004
Nanos Maintains Germline Stem Cell Self-Renewal by Preventing Differentiation
Wang Z, Lin H. Nanos Maintains Germline Stem Cell Self-Renewal by Preventing Differentiation. Science 2004, 303: 2016-2019. PMID: 14976263, DOI: 10.1126/science.1093983.Peer-Reviewed Original ResearchConceptsGermline stem cellsPrimordial germ cellsGermline cystsStem Cell Self-RenewalTranslational repressor NanosCell Self-RenewalStem cellsDrosophila ovaryGene regulationExtrinsic signalingPrecocious entrySelf-RenewalGerm cellsCell typesDifferentiation factorCellsCystoblastsOogenesisSignalingDifferentiationRegulationOvariesTranslation
2003
To be and not to be
Lin H. To be and not to be. Nature 2003, 425: 353-355. PMID: 14508468, DOI: 10.1038/425353a.Peer-Reviewed Original Research
2002
The stem-cell niche theory: lessons from flies
Lin H. The stem-cell niche theory: lessons from flies. Nature Reviews Genetics 2002, 3: 931-940. PMID: 12459723, DOI: 10.1038/nrg952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationDrosophilaFemaleMaleOvarySignal TransductionStem CellsTestisConceptsStem cell nicheSomatic stem cellsStem cellsTesticular stem cell nicheGermline stem cellsTerminal filament cellsSelf-renewing divisionsOogenic functionEpidermal growth factor receptorUnpaired ligandAdherens junctionsMammalian systemsTesticular nicheOvarian nicheGrowth factor receptorHub cellsPathway functionNiche theoryFilament cellsGermlineCell adhesionNicheFactor receptorPathwayFlies