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
The 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 markersEmbryogenesis
2018
MIWI2 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 RNAMethylationRNAPiRNAs
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
Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress
Ge XQ, Han J, Cheng EC, Yamaguchi S, Shima N, Thomas JL, Lin H. Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress. Stem Cell Reports 2015, 5: 185-194. PMID: 26190528, PMCID: PMC4618655, DOI: 10.1016/j.stemcr.2015.06.002.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsStem/progenitor cellsNeural stem/progenitor cellsStem cellsProgenitor cellsTissue stem/progenitor cellsMCM2-7 complexDNA replication originsTissue-specific stem/progenitor cellsStem cell typesGenome integrityGenomic integrityReplication stressDormant originsReplication forksReplicative stressDNA replicationReplication originsNeural lineagesDNA damageS phaseCell typesAbnormal neurogenesisCellsGenome
2014
Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline
Watanabe T, Cheng EC, Zhong M, Lin H. Retrotransposons and pseudogenes regulate mRNAs and lncRNAs via the piRNA pathway in the germline. Genome Research 2014, 25: 368-380. PMID: 25480952, PMCID: PMC4352877, DOI: 10.1101/gr.180802.114.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPiRNA pathwayRetrotransposon sequencesIntergenic regionMammalian PIWI-interacting RNAsRNA regulatory networkLate spermatocytesVivo functional analysisDegradation of mRNAUTR of mRNAsSlicer activityEukaryotic genomesLncRNA transcriptomeRegulatory networksRegulatory sequencesRepetitive sequencesPseudogenesMRNA stabilityFunctional analysisLncRNAsWidespread expressionSpermatid stageRetrotransposonsMRNATransposonPIWI 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 layers
2013
Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice
Nolde MJ, Cheng EC, Guo S, Lin H. Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice. PLOS ONE 2013, 8: e71950. PMID: 24058407, PMCID: PMC3751959, DOI: 10.1371/journal.pone.0071950.Peer-Reviewed Original ResearchConceptsPiwi genesHematopoietic stem cellsNormal adult hematopoiesisPIWI protein familyStem cellsStem/progenitor cellsDiverse organismsAdult hematopoiesisProtein familyLong-term hematopoiesisMyeloablative stressCompetitive transplantationTransient expressionHuman leukemia cell linesHSC compartmentLeukemia cell linesGenesProliferative stateNormal hematopoiesisCell typesMIWI2Progenitor cellsLineage reconstitutionHematopoiesisCell proliferationTdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline
Saxe JP, Chen M, Zhao H, Lin H. Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. The EMBO Journal 2013, 32: 1869-1885. PMID: 23714778, PMCID: PMC3981179, DOI: 10.1038/emboj.2013.121.Peer-Reviewed Original ResearchConceptsPrimary piRNA biogenesisPiRNA biogenesisKH domain-containing proteinPiRNA biogenesis pathwayPing-pong cycleDomain-containing proteinsMature piRNAsPIWI proteinsBiogenesis pathwayMitochondrial proteinsEpigenetic programmingNuclear localizationCytoplasmic localizationZygotene stageBiogenesisTDRKHArginine residuesMeiotic arrestMIWI2MIWIDistinct populationsProteinMutantsGermlineRNA
2012
piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism
Beyret E, Liu N, Lin H. piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell Research 2012, 22: 1429-1439. PMID: 22907665, PMCID: PMC3463270, DOI: 10.1038/cr.2012.120.Peer-Reviewed Original ResearchConceptsPIWI proteinsPing-pong mechanismSmall non-coding RNAsSame DNA strandNon-coding RNAsPiRNA biogenesisGermline developmentDiverse organismsEpigenetic regulationPiRNAsMIWIRepeat sequencesMILISame locusSequence featuresNucleotide positionsPostnatal testisBroad functionsAdult testisMouse testisDNA strandsAdult spermatogenesisProteinBiogenesisPrimary pathwayEssential Roles of the Chromatin Remodeling Factor Brg1 in Spermatogenesis in Mice1
Wang J, Gu H, Lin H, Chi T. Essential Roles of the Chromatin Remodeling Factor Brg1 in Spermatogenesis in Mice1. Biology Of Reproduction 2012, 86: 186, 1-10. PMID: 22495890, PMCID: PMC3386149, DOI: 10.1095/biolreprod.111.097097.Peer-Reviewed Original ResearchConceptsMeiotic recombinationSomatic cellsDNA repairMeiotic sex chromosome inactivationChromatin Remodeling Factor BRG1Sex chromosome inactivationChromatin-remodeling complexBAF chromatin-remodeling complexImpaired homologous recombinationEssential roleRole of BRG1Chromatin regulationChromatin structureFactor BRG1Male germlineMammalian spermatogenesisSpatiotemporal regulationChromosome inactivationCatalytic subunitHomologous recombinationMidpachytene stageBRG1Expression patternsGene expressionGerm cellsPumilio 1 Suppresses Multiple Activators of p53 to Safeguard Spermatogenesis
Chen D, Zheng W, Lin A, Uyhazi K, Zhao H, Lin H. Pumilio 1 Suppresses Multiple Activators of p53 to Safeguard Spermatogenesis. Current Biology 2012, 22: 420-425. PMID: 22342750, PMCID: PMC3449084, DOI: 10.1016/j.cub.2012.01.039.Peer-Reviewed Original Research
2011
Role for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus
Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H. Role for piRNAs and Noncoding RNA in de Novo DNA Methylation of the Imprinted Mouse Rasgrf1 Locus. Science 2011, 332: 848-852. PMID: 21566194, PMCID: PMC3368507, DOI: 10.1126/science.1203919.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsDNA MethylationGenomic ImprintingMaleMiceMice, Inbred C57BLMitochondrial ProteinsModels, GeneticMutationPhospholipase DProteinsRas-GRF1Repetitive Sequences, Nucleic AcidRetroelementsRNA, Small InterferingRNA, UntranslatedSpermatogoniaTestisTranscription, GeneticConceptsRasgrf1 locusDNA methylationPIWI-interacting RNA (piRNA) pathwayDe novo DNA methylationMonoallelic gene expressionNovo DNA methylationParental germ lineDe novo methylationSequence-specific methylationDifferential DNA methylationRNA pathwaysGenomic imprintingNovo methylationRetrotransposon sequencesGerm lineNoncoding RNAsGene expressionDirect repeatsPiRNAsTarget RNADifferent lociMethylationLociRNASpecific sequencesPinpointing the expression of piRNAs and function of the PIWI protein subfamily during spermatogenesis in the mouse
Beyret E, Lin H. Pinpointing the expression of piRNAs and function of the PIWI protein subfamily during spermatogenesis in the mouse. Developmental Biology 2011, 355: 215-226. PMID: 21539824, PMCID: PMC3443393, DOI: 10.1016/j.ydbio.2011.04.021.Peer-Reviewed Original ResearchConceptsPIWI proteinsXY bodyMouse testisAdult mouse testisEarly round spermatidsSex chromosomesGenomic sequencesPiRNAsChromatoid bodyCytological characterizationPachytene stageGerm cellsPhenotypic analysisAdult testisRound spermatidsProteinMeiosisSpermatogenesisCytoplasmDense bodiesSpermatocytesTestisPiRNAChromosomesTransposonMITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline
Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T, Noce T, Nakano T, Nakatsuji N, Lin H, Sasaki H. MITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline. Developmental Cell 2011, 20: 364-375. PMID: 21397847, PMCID: PMC3062204, DOI: 10.1016/j.devcel.2011.01.005.Peer-Reviewed Original ResearchConceptsPiRNA biogenesisDerepression of retrotransposonsPrimary piRNA biogenesisSmall RNA biogenesisMutant germ cellsMitochondrial protein essentialMicrotubule-dependent localizationPiRNA pathwayDrosophila homologRNA biogenesisConserved roleMitoPLDDiverse speciesProtein essentialPerinuclear structuresMouse germlineOuter membraneBiogenesisGerm cellsMeiotic arrestPhospholipase DMetabolism/Phosphatidic acidMitochondriaMutant mice
2010
Identification of Piwil2-Like (PL2L) Proteins that Promote Tumorigenesis
Ye Y, Yin DT, Chen L, Zhou Q, Shen R, He G, Yan Q, Tong Z, Issekutz AC, Shapiro CL, Barsky SH, Lin H, Li JJ, Gao JX. Identification of Piwil2-Like (PL2L) Proteins that Promote Tumorigenesis. PLOS ONE 2010, 5: e13406. PMID: 20975993, PMCID: PMC2958115, DOI: 10.1371/journal.pone.0013406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsBase SequenceCell Line, TumorCell Transformation, NeoplasticDNA PrimersFemaleHumansImmunohistochemistryMaleMiceMice, Inbred C57BLNeoplasm MetastasisNeoplasmsNF-kappa BPrecancerous ConditionsProteinsProto-Oncogene Proteins c-bcl-2Reverse Transcriptase Polymerase Chain ReactionRNA InterferenceRNA, MessengerSTAT3 Transcription FactorStem CellsTransplantation, HeterologousUp-RegulationConceptsGermline stem cellsStem cellsAGO gene familyCell cycle entryPrecancerous stem cellsTumor developmentTumor cell survivalBCL2 gene expressionGene familyCycle entryGene expressionTumor cellsNF-κBCell survivalAnticancer drug developmentPIWIL2S phaseGene exonsNovel insightsProteinMouse tumor cellsCancer developmentNovel monoclonal antibodyTranscriptsTypes of human