TY - JOUR
T1 - Human brain organoids assemble functionally integrated bilateral optic vesicles
AU - Gabriel, Elke
AU - Albanna, Walid
AU - Pasquini, Giovanni
AU - Ramani, Anand
AU - Josipovic, Natasa
AU - Mariappan, Aruljothi
AU - Schinzel, Friedrich
AU - Karch, Celeste M.
AU - Bao, Guobin
AU - Gottardo, Marco
AU - Suren, Ata Alp
AU - Hescheler, Jürgen
AU - Nagel-Wolfrum, Kerstin
AU - Persico, Veronica
AU - Rizzoli, Silvio O.
AU - Altmüller, Janine
AU - Riparbelli, Maria Giovanna
AU - Callaini, Giuliano
AU - Goureau, Olivier
AU - Papantonis, Argyris
AU - Busskamp, Volker
AU - Schneider, Toni
AU - Gopalakrishnan, Jay
N1 - Funding Information:
We thank Helen May Simura and Eugenio F. Fornasiero for discussions. We thank E. Paccagnini for help with the scanning electron microscope. We acknowledge our use of the GSEA software and C5 Molecular Signature Database (MsigDB; Subramanian et al., 2005 ; https://www.broadinstitute.org/gsea/ ). We are thankful to Peter Davies for PHF-1. This study was supported by Deutsche Forschungsgemeinschaft , SPP2127 (to J.G. and V.B.), EXC-2151-390873048–Cluster of Excellence– ImmunoSensation2 at the University of Bonn (to V.B.), SPP1935 (to N.J. and A.P.) and by the Fritz Thyssen Stiftung (to E.G. and J.G.).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/10/7
Y1 - 2021/10/7
N2 - 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.
AB - 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.
KW - FOXG1
KW - OVB-organoids
KW - brain organoids
KW - forebrain organoids
KW - iPSCs
KW - optic vesicles
KW - primary cilium
KW - primordial eye fields
KW - retinal pigment epithelium
UR - http://www.scopus.com/inward/record.url?scp=85115371162&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2021.07.010
DO - 10.1016/j.stem.2021.07.010
M3 - Article
C2 - 34407456
AN - SCOPUS:85115371162
VL - 28
SP - 1740-1757.e8
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 10
ER -