2024
42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS
Seah C, Signer R, Young H, Hicks E, Rusielewicz T, Bader H, Xu C, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. 42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS. European Neuropsychopharmacology 2024, 87: 71-72. DOI: 10.1016/j.euroneuro.2024.08.156.Peer-Reviewed Original ResearchPost-mortem brainsTranscription factor binding sitesAbsence of cellular stressCombat-exposed veteransFactor binding sitesImpact gene expressionBinding sitesGR binding sitesPositive regulatory activityMotif enrichmentSequence readsCRISPRi screenOpen chromatinFunctional annotationBrain regionsTraumatic stressCRISPR screensEQTLTraumatic experiencesLeading locusPTSDPerturbed genesRegulatory architectureTranscriptomic activityTranscriptomic responseSingle-cell genomics and regulatory networks for 388 human brains
Emani P, Liu J, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee C, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X, Bakken T, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard J, Gancz M, Garrido-MartÃn D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman G, Huang A, Jiang Y, Jin T, Jorstad N, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran J, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan A, Riesenmy T, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini K, Wamsley B, Wang G, Xia Y, Xiao S, Yang A, Zheng S, Gandal M, Lee D, Lein E, Roussos P, Sestan N, Weng Z, White K, Won H, Girgenti M, Zhang J, Wang D, Geschwind D, Gerstein M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Berretta S, Bharadwaj R, Bhattacharya A, Brennand K, Capauto D, Champagne F, Chatzinakos C, Chen H, Cheng L, Chess A, Chien J, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duong D, Eagles N, Edelstein J, Galani K, Girdhar K, Goes F, Greenleaf W, Guo H, Guo Q, Hadas Y, Hallmayer J, Han X, Haroutunian V, He C, Hicks S, Ho M, Ho L, Huang Y, Huuki-Myers L, Hyde T, Iatrou A, Inoue F, Jajoo A, Jiang L, Jin P, Jops C, Jourdon A, Kellis M, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Li J, Li M, Lin X, Liu S, Liu C, Loupe J, Lu D, Ma L, Mariani J, Martinowich K, Maynard K, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Mukamel E, Nairn A, Nemeroff C, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Pinto D, Pochareddy S, Pollard K, Pollen A, Przytycki P, Purmann C, Qin Z, Qu P, Raj T, Reach S, Reimonn T, Ressler K, Ross D, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Seyfried N, Shao Z, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wang T, Wang S, Wang Y, Wei Y, Weimer A, Weinberger D, Wen C, Whalen S, Willsey A, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang Y, Ziffra R, Zeier Z, Zintel T. Single-cell genomics and regulatory networks for 388 human brains. Science 2024, 384: eadi5199. PMID: 38781369, PMCID: PMC11365579, DOI: 10.1126/science.adi5199.Peer-Reviewed Original ResearchConceptsSingle-cell genomicsSingle-cell expression quantitative trait locusExpression quantitative trait lociDrug targetsQuantitative trait lociPopulation-level variationSingle-cell expressionCell typesDisease-risk genesTrait lociGene familyRegulatory networksGene expressionCell-typeMultiomics datasetsSingle-nucleiGenomeGenesCellular changesHeterogeneous tissuesExpressionCellsChromatinLociMultiomics209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling
Seah C, Devarajan A, Jurczyszak D, Chakka A, Huckins L, Brennand K, Girgenti M. 209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling. Neurosurgery 2024, 70: 55-56. DOI: 10.1227/neu.0000000000002809_209.Peer-Reviewed Original ResearchIntracranial atherosclerotic stenosisIntracranial arteriesInterferon-inducible genesInterferon signalingPeripheral atherosclerosisCerebral atherosclerosisExpression of interferon-inducible genesGlial cellsSymptomatic intracranial atherosclerotic stenosisInduced pluripotent stem cellsPost-mortem brainsWorsened functional outcomesHuman induced pluripotent stem cellsUpregulation of interferon inducible genesCause of ischemic strokePluripotent stem cellsRisk of atherosclerosisLipid-rich plaquesRisk factor managementClinical outcomesPoor prognosisExcitatory neuronsIncreased morbidityHistopathological profileFunctional outcomes
2023
STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD
Seah C, Signer R, Young H, Kozik E, Rusielewicz T, Bader H, Xu C, de Pins A, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. STRESS IN A DISH: MODELING THE IMPACT OF COMMON GENETIC VARIATION ON STRESS RESPONSE IN HIPSC-DERIVED NEURONS IN PTSD. European Neuropsychopharmacology 2023, 75: s40. DOI: 10.1016/j.euroneuro.2023.08.081.Peer-Reviewed Original ResearchCommon genetic variationGenetic variationStress responseCell typesEQTL associationsTranscriptional stress responseGenomic risk lociTissue-specific mannerChIP-seq datasetsCell type deconvolutionCommon genetic variantsPost-mortem brainsGene expression signaturesHiPSC-derived neuronsTranscription factorsSuch lociCatalog genesRisk lociGenetic studiesExpression signaturesGenetic variantsRegulatory activityGenesEQTLsMechanistic understandingModeling Gene by Environment Interactions in Post-Traumatic Stress Disorder Across the Post-Mortem Brain and in hiPSC-Derived Neurons
Seah C, Signer R, Young H, Rusielewicz T, Bader H, Xu C, dePins A, Breen M, Paull D, Girgenti M, Yehuda R, Brennand K, Huckins L. Modeling Gene by Environment Interactions in Post-Traumatic Stress Disorder Across the Post-Mortem Brain and in hiPSC-Derived Neurons. Biological Psychiatry 2023, 93: s11. DOI: 10.1016/j.biopsych.2023.02.048.Peer-Reviewed Original ResearchIntegrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings
Hicks E, Seah C, Cote A, Marchese S, Brennand K, Nestler E, Girgenti M, Huckins L. Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings. Translational Psychiatry 2023, 13: 129. PMID: 37076454, PMCID: PMC10115809, DOI: 10.1038/s41398-023-02412-7.Peer-Reviewed Original ResearchConceptsBioinformatics approachTranscriptomic dataBrain transcriptomeGenome-wide analysisDynamic transcriptional landscapeBrain gene expression dataGene expression dataTranscriptional landscapeTranscriptomic studiesIntegrating GeneticExpression dataPhenotypic signaturesGenomic driversTranscriptomeMajor depressive disorderValuable resourceRecent findingsEnvironmental influencesTranscriptomicsDepressive disorderGeneticsMultiple approachesPathophysiology of depressionSignaturesDysregulation
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