2024
Massively parallel characterization of regulatory elements in the developing human cortex
Deng C, Whalen S, Steyert M, Ziffra R, Przytycki P, Inoue F, Pereira D, Capauto D, Norton S, Vaccarino F, Pollen A, Nowakowski T, Ahituv N, Pollard K, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Bendl J, Berretta S, Bharadwaj R, Bhattacharya A, Bicks L, Brennand K, Capauto D, Champagne F, Chatterjee T, Chatzinakos C, Chen Y, Chen H, Cheng Y, Cheng L, Chess A, Chien J, Chu Z, Clarke D, 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, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Fullard J, Galani K, Galeev T, Gandal M, Gaynor S, Gerstein M, Geschwind D, Girdhar K, Goes F, Greenleaf W, Grundman J, Guo H, Guo Q, Gupta C, Hadas Y, Hallmayer J, Han X, Haroutunian V, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, Hoffman G, Huang Y, Huuki-Myers L, Hwang A, Hyde T, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kellis M, Khullar S, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Lee C, Lee D, Li J, Li M, Lin X, Liu S, Liu J, Liu J, Liu C, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Margolis M, Mariani J, Martinowich K, Maynard K, Mazariegos S, Meng R, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Moore J, Moran J, Mukamel E, Nairn A, Nemeroff C, Ni P, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollard K, Pollen A, Pratt H, Przytycki P, Purmann C, Qin Z, Qu P, Quintero D, Raj T, Rajagopalan A, Reach S, Reimonn T, Ressler K, Ross D, Roussos P, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Sestan N, Seyfried N, Shao Z, Shedd N, 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, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Weinberger D, Wen C, Weng Z, Whalen S, White K, Willsey A, Won H, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Xu S, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Massively parallel characterization of regulatory elements in the developing human cortex. Science 2024, 384: eadh0559. PMID: 38781390, DOI: 10.1126/science.adh0559.Peer-Reviewed Original ResearchConceptsGene regulatory elementsRegulatory elementsRegulation of enhancer activityCharacterization of regulatory elementsCis-regulatory activityNeuronal developmentPrimary cellsEnhanced activityGene regulationHuman neuronal developmentNucleotide changesEnhancer sequencesSequence basisUpstream regulatorComprehensive catalogHuman cellsDeveloping cortexSequenceVariantsOrganoidsCellsCerebral organoidsCortexHuman cortexNucleotide
2017
High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain
Zhou T, Tan L, Cederquist G, Fan Y, Hartley B, Mukherjee S, Tomishima M, Brennand K, Zhang Q, Schwartz R, Evans T, Studer L, Chen S. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain. Cell Stem Cell 2017, 21: 274-283.e5. PMID: 28736217, PMCID: PMC5553280, DOI: 10.1016/j.stem.2017.06.017.Peer-Reviewed Original ResearchConceptsZIKV infectionNeurological complicationsZika virusZIKV-infected patientsSerious neurological complicationsZika virus infectionCortical neural progenitor cellsForebrain organoidsAdult mouse brainHigh-content chemical screenDrug candidatesNeural progenitor cellsAdult patientsHuman forebrain organoidsVirus infectionMouse modelAdult brainAdult miceMouse brainTherapeutic potentialTherapeutic treatmentInfectionProgenitor cellsBrainComplications
2016
Neural organoids for disease phenotyping, drug screening and developmental biology studies
Hartley B, Brennand K. Neural organoids for disease phenotyping, drug screening and developmental biology studies. Neurochemistry International 2016, 106: 85-93. PMID: 27744003, PMCID: PMC5389930, DOI: 10.1016/j.neuint.2016.10.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman induced pluripotent stem cellsNeural organoidsCell-extracellular matrix interactionsCell typesDevelopmental biology studiesSpecific physiological functionsCell-cell interactionsInduced pluripotent stem cellsNervous system cell typesCentral nervous system cell typesPluripotent stem cellsCell replacement therapyBiology studiesCurrent biomedical researchDifferentiation protocolsPhysiological functionsComplex tissuesMatrix interactionsNovel technological platformStem cellsDisease mechanismsSpatial organizationUnknown disease mechanismsToxicity assaysHeterogeneous tissuesIdentification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen
Xu M, Lee E, Wen Z, Cheng Y, Huang W, Qian X, TCW J, Kouznetsova J, Ogden S, Hammack C, Jacob F, Nguyen H, Itkin M, Hanna C, Shinn P, Allen C, Michael S, Simeonov A, Huang W, Christian K, Goate A, Brennand K, Huang R, Xia M, Ming G, Zheng W, Song H, Tang H. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nature Medicine 2016, 22: 1101-1107. PMID: 27571349, PMCID: PMC5386783, DOI: 10.1038/nm.4184.Peer-Reviewed Original Research