Human brain organoids assemble functionally integrated bilateral optic vesicles

Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasa Josipovic, Aruljothi Mariappan, Friedrich Schinzel, Celeste M. Karch, Guobin Bao, Marco Gottardo, Ata Alp Suren, Jürgen Hescheler, Kerstin Nagel-Wolfrum, Veronica Persico, Silvio O. Rizzoli, Janine Altmüller, Maria Giovanna Riparbelli, Giuliano Callaini, Olivier Goureau, Argyris PapantonisVolker Busskamp, Toni Schneider, Jay Gopalakrishnan

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1740-1757.e8
JournalCell Stem Cell
Volume28
Issue number10
DOIs
StatePublished - Oct 7 2021

Keywords

  • FOXG1
  • OVB-organoids
  • brain organoids
  • forebrain organoids
  • iPSCs
  • optic vesicles
  • primary cilium
  • primordial eye fields
  • retinal pigment epithelium

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