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 Papantonis; Volker Busskamp; Toni Schneider; Jay Gopalakrishnan

doi:10.1016/j.stem.2021.07.010

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 journal › Article › peer-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 language	English
Pages (from-to)	1740-1757.e8
Journal	Cell Stem Cell
Volume	28
Issue number	10
DOIs	https://doi.org/10.1016/j.stem.2021.07.010
State	Published - 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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10.1016/j.stem.2021.07.010

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Gabriel, E., Albanna, W., Pasquini, G., Ramani, A., Josipovic, N., Mariappan, A., Schinzel, F., Karch, C. M., Bao, G., Gottardo, M., Suren, A. A., Hescheler, J., Nagel-Wolfrum, K., Persico, V., Rizzoli, S. O., Altmüller, J., Riparbelli, M. G., Callaini, G., Goureau, O., ... Gopalakrishnan, J. (2021). Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell, 28(10), 1740-1757.e8. https://doi.org/10.1016/j.stem.2021.07.010

Gabriel, Elke ; Albanna, Walid ; Pasquini, Giovanni ; Ramani, Anand ; Josipovic, Natasa ; Mariappan, Aruljothi ; Schinzel, Friedrich ; Karch, Celeste M. ; Bao, Guobin ; Gottardo, Marco ; Suren, Ata Alp ; Hescheler, Jürgen ; Nagel-Wolfrum, Kerstin ; Persico, Veronica ; Rizzoli, Silvio O. ; Altmüller, Janine ; Riparbelli, Maria Giovanna ; Callaini, Giuliano ; Goureau, Olivier ; Papantonis, Argyris ; Busskamp, Volker ; Schneider, Toni ; Gopalakrishnan, Jay. / Human brain organoids assemble functionally integrated bilateral optic vesicles. In: Cell Stem Cell. 2021 ; Vol. 28, No. 10. pp. 1740-1757.e8.

@article{eb51bc653b36400f8a63613b448348ec,

title = "Human brain organoids assemble functionally integrated bilateral optic vesicles",

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.",

keywords = "FOXG1, OVB-organoids, brain organoids, forebrain organoids, iPSCs, optic vesicles, primary cilium, primordial eye fields, retinal pigment epithelium",

author = "Elke Gabriel and Walid Albanna and Giovanni Pasquini and Anand Ramani and Natasa Josipovic and Aruljothi Mariappan and Friedrich Schinzel and Karch, {Celeste M.} and Guobin Bao and Marco Gottardo and Suren, {Ata Alp} and J{\"u}rgen Hescheler and Kerstin Nagel-Wolfrum and Veronica Persico and Rizzoli, {Silvio O.} and Janine Altm{\"u}ller and Riparbelli, {Maria Giovanna} and Giuliano Callaini and Olivier Goureau and Argyris Papantonis and Volker Busskamp and Toni Schneider and Jay Gopalakrishnan",

note = "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: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = oct,

day = "7",

doi = "10.1016/j.stem.2021.07.010",

language = "English",

volume = "28",

pages = "1740--1757.e8",

journal = "Cell Stem Cell",

issn = "1934-5909",

number = "10",

}

Gabriel, E, Albanna, W, Pasquini, G, Ramani, A, Josipovic, N, Mariappan, A, Schinzel, F, Karch, CM, Bao, G, Gottardo, M, Suren, AA, Hescheler, J, Nagel-Wolfrum, K, Persico, V, Rizzoli, SO, Altmüller, J, Riparbelli, MG, Callaini, G, Goureau, O, Papantonis, A, Busskamp, V, Schneider, T & Gopalakrishnan, J 2021, 'Human brain organoids assemble functionally integrated bilateral optic vesicles', Cell Stem Cell, vol. 28, no. 10, pp. 1740-1757.e8. https://doi.org/10.1016/j.stem.2021.07.010

Human brain organoids assemble functionally integrated bilateral optic vesicles. / Gabriel, Elke; Albanna, Walid; Pasquini, Giovanni; Ramani, Anand; Josipovic, Natasa; Mariappan, Aruljothi; Schinzel, Friedrich; Karch, Celeste M.; Bao, Guobin; Gottardo, Marco; Suren, Ata Alp; Hescheler, Jürgen; Nagel-Wolfrum, Kerstin; Persico, Veronica; Rizzoli, Silvio O.; Altmüller, Janine; Riparbelli, Maria Giovanna; Callaini, Giuliano; Goureau, Olivier; Papantonis, Argyris; Busskamp, Volker; Schneider, Toni; Gopalakrishnan, Jay.

In: Cell Stem Cell, Vol. 28, No. 10, 07.10.2021, p. 1740-1757.e8.

Research output: Contribution to journal › Article › peer-review

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 -

Human brain organoids assemble functionally integrated bilateral optic vesicles

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Keywords

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