2022
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus
Duy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventricular dilatationPrimary defectNeuroepithelial cell differentiationRisk genesCerebrospinal fluid homeostasisWhole-exome sequencingNeuroepithelial stem cellsCortical hypoplasiaReduced neurogenesisVentricular dilatationVentricular enlargementCH mutationsPrenatal hydrocephalusDisease heterogeneityBrain surgeryCSF circulationHydrocephalusGenetic subtypesFluid homeostasisNeuroepithelial cellsNovo mutationsBrain transcriptomicsStem cellsCell differentiationPUMILIO proteins promote colorectal cancer growth via suppressing p21
Gong Y, Liu Z, Yuan Y, Yang Z, Zhang J, Lu Q, Wang W, Fang C, Lin H, Liu S. PUMILIO proteins promote colorectal cancer growth via suppressing p21. Nature Communications 2022, 13: 1627. PMID: 35338151, PMCID: PMC8956581, DOI: 10.1038/s41467-022-29309-1.Peer-Reviewed Original ResearchConceptsColorectal cancerAOM/DSS modelIntestine-specific knockoutColitis-associated cancerHuman CRC cellsOrthotopic colon cancer modelColorectal cancer growthG1/S transitionHuman colorectal cancerColorectal tumor growthColon cancer modelCancer cell growthCRC progressionCRC cellsIntravenous injectionTherapeutic targetCancer growthCancer modelTumor growthSignificant decreaseS transitionDirect targetP21 mRNACancerDSS model
2021
Maternal Piwi regulates primordial germ cell development to ensure the fertility of female progeny in Drosophila
Gonzalez LE, Tang X, Lin H. Maternal Piwi regulates primordial germ cell development to ensure the fertility of female progeny in Drosophila. Genetics 2021, 219: iyab091. PMID: 34142134, PMCID: PMC8757300, DOI: 10.1093/genetics/iyab091.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsGermline developmentPiwi knockdownPIWI proteinsEarly embryosPiwi/piRNA complexesPIWI/piRNA pathwayFemale progenyPrimordial germ cell developmentGermline sex determinationLoss of PiwiGermline stem cellsDrosophila early embryosGerm cell developmentGerm cell proliferationGonad coalescencePiRNA complexesPiRNA pathwayPiRNA poolTransposon suppressionZygotic genesEmbryonic germlineEmbryonic functionEarly embryogenesisPiwiRoles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs
Wang C, Lin H. Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs. Genome Biology 2021, 22: 27. PMID: 33419460, PMCID: PMC7792047, DOI: 10.1186/s13059-020-02221-x.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPIWI proteinsRole of piRNAsPIWI-piRNA pathwayRNA-binding proteinSmall noncoding RNAsGermline mRNAsGermline developmentNoncoding RNAsRegulatory relationshipsGerm cellsRNAProteinTransposonMajor classesRNA levelsRecent studiesExpressionGenomeSubfamiliesGermlineLncRNAsMajor constituentsMRNARegulationGenome-wide mapping of Piwi association with specific loci in Drosophila ovaries
Liu N, Neuenkirchen N, Zhong M, Lin H. Genome-wide mapping of Piwi association with specific loci in Drosophila ovaries. G3: Genes, Genomes, Genetics 2021, 11: jkaa059. PMID: 33609367, PMCID: PMC8022938, DOI: 10.1093/g3journal/jkaa059.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsProtein-coding genesDrosophila ovaryGermline stem cell maintenanceRole of piRNAsTermination sitesGenome-wide mappingGenomic binding profileTranscriptional termination sitesSpecific genomic sitesStem cell maintenanceRNA pathwaysTransposon repressionTranscriptional startEuchromatic regionsGene regulationEpigenetic regulationGenomic sitesCell maintenancePiwiSpecific lociMethylation signalsDiverse mechanismsTarget siteBinding sitesThe Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis
Cheng EC, Hsieh CL, Liu N, Wang J, Zhong M, Chen T, Li E, Lin H. The Essential Function of SETDB1 in Homologous Chromosome Pairing and Synapsis during Meiosis. Cell Reports 2021, 34: 108575. PMID: 33406415, PMCID: PMC8513770, DOI: 10.1016/j.celrep.2020.108575.Peer-Reviewed Original ResearchConceptsEarly meiosisEarly meiotic prophase IFunction of SETDB1Homologous chromosome pairingMeiotic prophase IHistone-lysine N-methyltransferaseMeiotic silencingSurvival of spermatocytesGermline developmentBouquet formationHomologous chromosomesLineage genesChromosome pairingBivalent formationPericentromeric regionProphase IApoptosis of spermatocytesSETDB1Essential functionsHomologous bivalentsH3K9me3Meiotic arrestMeiosisSpermatocytesN-methyltransferase
2020
PIWIL1 promotes gastric cancer via a piRNA-independent mechanism
Shi S, Yang ZZ, Liu S, Yang F, Lin H. PIWIL1 promotes gastric cancer via a piRNA-independent mechanism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 22390-22401. PMID: 32848063, PMCID: PMC7486755, DOI: 10.1073/pnas.2008724117.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPIWI proteinsGastric cancer cellsNonsense-mediated mRNA decay mechanismPiRNA-independent mechanismDomain protein familyMRNA decay mechanismMammalian somatic tissuesRNA deep sequencingGastric cancer cell line SNU-1Cancer cellsGastric cancer cell proliferationRNA pathwaysPPD proteinsProtein familyPiwil1 geneSomatic tissuesSomatic cancersCancer cell proliferationDeep sequencingRegulatory mechanismsOncogenic functionPIWIL1Gastric cancer tissuesDetectable functionMIWI prevents aneuploidy during meiosis by cleaving excess satellite RNA
Hsieh C, Xia J, Lin H. MIWI prevents aneuploidy during meiosis by cleaving excess satellite RNA. The EMBO Journal 2020, 39: embj2019103614. PMID: 32677148, PMCID: PMC7429737, DOI: 10.15252/embj.2019103614.Peer-Reviewed Original ResearchConceptsChromosome misalignmentSatellite RNAKinetochore assemblySatellite repeatsWild-type spermatocytesPericentromeric satellite repeatsFaithful chromosome segregationProper kinetochore assemblyChromosome mis-segregationPost-transcriptional regulationPiRNA biogenesisMeiotic functionsPIWI proteinsChromosome segregationMis-segregationMurine memberElevated aneuploidyMale meiosisPrevents aneuploidyDicer cleavageMIWIMetaphase IRNA fragmentsMeiosisRNAPumilio 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 markersEmbryogenesisPIWI–piRNA pathway-mediated transposable element repression in Hydra somatic stem cells
Teefy BB, Siebert S, Cazet JF, Lin H, Juliano CE. PIWI–piRNA pathway-mediated transposable element repression in Hydra somatic stem cells. RNA 2020, 26: 550-563. PMID: 32075940, PMCID: PMC7161359, DOI: 10.1261/rna.072835.119.Peer-Reviewed Original ResearchConceptsPIWI-piRNA pathwayTE expressionSomatic stem cellsTransposable elementsTE transcriptsStem cellsFreshwater cnidarianSmall RNA pathwaysTransposable element repressionSomatic cell lineagesGermline of animalsInterstitial stem cellsStem cell populationInterstitial lineageSomatic piRNAsDegradome sequencingEpithelial cellsAncestral functionRNA pathwaysGermline piRNAsPIWI proteinsTE repressionGermline competenceSequence signaturesRNA immunoprecipitation
2019
Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea
Wang C, Yang ZZ, Guo FH, Shi S, Han XS, Zeng A, Lin H, Jing Q. Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea. Journal Of Biological Chemistry 2019, 294: 9873-9887. PMID: 31076507, PMCID: PMC6597837, DOI: 10.1074/jbc.ra118.004445.Peer-Reviewed Original ResearchConceptsPIWI proteinsPIWI-interacting RNA (piRNA) biogenesisPlanarian adult stem cellsHeat shock protein 40 family membersDifferent evolutionary lineagesPlanarian Schmidtea mediterraneaStem cell maintenanceStem cell regulationCo-immunoprecipitation assaysStem cellsSomatic stem cellsControl of proteinAdult stem cellsHuman gastric cancer cellsPiRNA biogenesisRNA biogenesisEvolutionary lineagesPiwi-like RNASchmidtea mediterraneaTwo-hybridSMEDWI-1Planarian speciesCell maintenanceGastric cancer cellsPlanarian regeneration
2018
The Role of Maternal HP1a in Early Drosophila Embryogenesis via Regulation of Maternal Transcript Production
Park AR, Liu N, Neuenkirchen N, Guo Q, Lin H. The Role of Maternal HP1a in Early Drosophila Embryogenesis via Regulation of Maternal Transcript Production. Genetics 2018, 211: 201-217. PMID: 30442760, PMCID: PMC6325692, DOI: 10.1534/genetics.118.301704.Peer-Reviewed Original ResearchConceptsHeterochromatin protein 1aMaternal transcriptsEarly Drosophila embryogenesisGermline developmentDrosophila embryogenesisMRNA splicingCell divisionTranscript productionProtein 1AEpigenetic factorsDownregulates genesEmbryogenesisGenesTranscriptsSplicingOogenesisTranscriptionOrganogenesisRegulationRoleProductionNeurogenesisDivisionDevelopmentTranslationMIWI2 targets RNAs transcribed from piRNA‐dependent regions to drive DNA methylation in mouse prospermatogonia
Watanabe T, Cui X, Yuan Z, Qi H, Lin H. MIWI2 targets RNAs transcribed from piRNA‐dependent regions to drive DNA methylation in mouse prospermatogonia. The EMBO Journal 2018, 37: embj201695329. PMID: 30108053, PMCID: PMC6138435, DOI: 10.15252/embj.201695329.Peer-Reviewed Original ResearchConceptsDNA methylationRetrotransposon sequencesSmall RNAsArgonaute/Piwi proteinsPiwi protein MIWI2Suppressive epigenetic marksMouse prospermatogoniaChromatin statePIWI proteinsUnderlying molecular mechanismsDiverse organismsEpigenetic marksPiRNA clustersNascent RNAEpigenetic regulationTranslational regulationMIWI2RNA degradationRepeat sequencesGene expressionMolecular mechanismsTarget RNAMethylationRNAPiRNAsmiR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer
Liu S, Wang Z, Liu Z, Shi S, Zhang Z, Zhang J, Lin H. miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer. Journal Of Molecular Cell Biology 2018, 10: 302-315. PMID: 30053090, DOI: 10.1093/jmcb/mjy041.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerWnt/β-cateninMiR-221/222 expressionTNBC cell linesBreast cancerMiR-221/222Β-cateninHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Progression of TNBCGrowth factor receptor 2Limited treatment optionsWnt/β-catenin activationNegative breast cancerFactor receptor 2Primary tumor samplesWnt/β-catenin signalingCell linesWnt3a treatmentMultiple negative regulatorsΒ-catenin activationΒ-catenin signalingPatient survivalPoor prognosisTreatment optionsA critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila
Parikh RY, Lin H, Gangaraju VK. A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila. Journal Of Biological Chemistry 2018, 293: 9140-9147. PMID: 29735528, PMCID: PMC6005430, DOI: 10.1074/jbc.ac118.003264.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsArgonaute ProteinsDNA Transposable ElementsDrosophilaDrosophila ProteinsFemaleGene Expression RegulationGene SilencingGenomic InstabilityGerm CellsMaleMolecular ChaperonesNuclear Pore Complex ProteinsProtein Interaction MapsRNA, Small InterferingTranscription, GeneticConceptsPIWI-interacting RNAsPing-pong cycleNuclear pore complexPiRNA biogenesisGermline knockdownPiRNA pathwayAntisense Piwi-interacting RNAsPiRNA precursor transcriptionSmall noncoding RNAsPiwi functionSilence transposonsPIWI proteinsShort hairpin RNACritical roleArgonaute 3Pore complexNoncoding RNAsGenomic instabilityNuclear localizationGene expressionTransposonNup358Germ cellsBiogenesisHairpin RNA
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
2016
An Important Role of Pumilio 1 in Regulating the Development of the Mammalian Female Germline1
Mak W, Fang C, Holden T, Dratver MB, Lin H. An Important Role of Pumilio 1 in Regulating the Development of the Mammalian Female Germline1. Biology Of Reproduction 2016, 94: 134, 1-11. PMID: 27170441, PMCID: PMC4946805, DOI: 10.1095/biolreprod.115.137497.Peer-Reviewed Original ResearchConceptsPumilio 1PUF proteinsLate meiotic prophase IPumilio/FBF (PUF) proteinReproductive competencyPrimordial follicle poolFemale germ cell developmentMammalian germ cellsPrimordial folliculogenesisFemale reproductive competenceMeiotic prophase IGerm cell developmentFBF proteinsGermline establishmentTranslational regulatorTranslational regulationProphase IDiplotene stageCell developmentGerm cellsFollicle poolImportant roleDetectable functionMammalsReproductive competenceTudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila
Ku HY, Gangaraju VK, Qi H, Liu N, Lin H. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila. PLOS Genetics 2016, 12: e1005813. PMID: 26808625, PMCID: PMC4726654, DOI: 10.1371/journal.pgen.1005813.Peer-Reviewed Original ResearchConceptsPiRNA biogenesisPrimordial germ cellsPiwi expressionTudor-SNSomatic cellsGerm cellsDiverse molecular functionsPost-transcriptional regulationEmbryonic somatic cellsPiwi mutantsDosage-dependent mannerGermline developmentPIWI proteinsMutant phenotypeMeiotic cytokinesisMolecular functionsSpliceosome assemblyPiwiEpigenetic programmingDiverse functionsBiological functionsAdult ovariesBiogenesisTransposonMale fertilityPiwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins
Peng JC, Valouev A, Liu N, Lin H. Piwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins. Nature Genetics 2016, 48: 283-291. PMID: 26780607, PMCID: PMC4767590, DOI: 10.1038/ng.3486.Peer-Reviewed Original Research
2015
Poreless eggshells
Lin H, Matzuk MM. Poreless eggshells. Journal Of Clinical Investigation 2015, 125: 4005-4007. PMID: 26485282, PMCID: PMC4639988, DOI: 10.1172/jci84692.Peer-Reviewed Original ResearchConceptsNuclear pore complex functionMissense mutationsSpecific amino acid changesAmino acid changesRecessive missense mutationSomatic cellsNucleoporin 107Human mutationsGenetic materialAcid changesExtragonadal functionsOvarian developmentOocyte developmentMutationsGenesSole sourceFemale genetic materialIntrinsic factorsComplex functionsOrthologsAbnormal ovarian developmentFollicular developmentEmbryosFliesOocytes