6533b854fe1ef96bd12ae97a

RESEARCH PRODUCT

Human brain organoids assemble functionally integrated bilateral optic vesicles

Ata Alp SurenGuobin BaoArgyris PapantonisAnand RamaniAruljothi MariappanWalid AlbannaWalid AlbannaSilvio O. RizzoliKerstin Nagel-wolfrumOlivier GoureauToni SchneiderMaria Giovanna RiparbelliVolker BusskampFriedrich SchinzelElke GabrielMarco GottardoJürgen HeschelerGiovanni PasquiniNatasa JosipovicNatasa JosipovicVeronica PersicoJay GopalakrishnanJanine AltmüllerCeleste M. KarchGiuliano Callaini

subject

OrganogenesisInduced Pluripotent Stem Cellsretinal pigment epitheliumiPSCsEmbryonic DevelopmentBiology03 medical and health sciencesDiencephalonchemistry.chemical_compoundProsencephalon0302 clinical medicineGeneticsOrganoidmedicineHumansInduced pluripotent stem cell030304 developmental biology0303 health sciencesforebrain organoidsRetinal pigment epitheliumbrain organoidsVesicleprimordial eye fieldsOVB-organoidsCell DifferentiationRetinalCell BiologyOptic vesicleHuman brainCell biologyOrganoidsmedicine.anatomical_structurenervous systemchemistryMolecular MedicineFOXG1; OVB-organoids; brain organoids; forebrain organoids; iPSCs; optic vesicles; primary cilium; primordial eye fields; retinal pigment epitheliumoptic vesiclesFOXG1030217 neurology & neurosurgeryprimary cilium

description

During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human brain organoids, we attempted to simplify the complexities and demonstrate formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day 30, brain organoids attempt to assemble optic vesicles, which develop progressively as visible structures within 60 days. These optic vesicle-containing brain organoids (OVB-organoids) constitute a developing optic vesicle's cellular components, including primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. OVB-organoids also display synapsin-1, CTIP-positive myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photosensitive activity of OVB-organoids, and light sensitivities could be reset after transient photobleaching. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow interorgan interaction studies within a single organoid.

https://doi.org/10.1016/j.stem.2021.07.010