Generation of iPSC-derived human forebrain organoids assembling bilateral eye primordia

Volker Busskamp, Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasa Josipovic, Aruljothi Mariappan, Maria Giovanna Riparbelli, Giuliano Callaini, Celeste M. Karch, Olivier Goureau, Argyris Papantonis, Toni Schneider, Jay Gopalakrishnan

Published: 2023-05-16 DOI: 10.1038/s41596-023-00814-x

human forebrain organoids

iPSC-derived

optic vesicles

neural differentiation

3D organoid culture

AI 解读

Opto-juxtacellular interrogation of neural circuits in freely moving mice

Generation of iPSC-derived human forebrain organoids assembling bilateral eye primordia

Self-assembled ultraflexible probes for long-term neural recordings and neuromodulation

Acute head-fixed recordings in awake mice with multiple Neuropixels probes

Creating hierarchical pores in metal–organic frameworks via postsynthetic reactions

SorTn-seq: a high-throughput functional genomics approach to discovering regulators of bacterial gene expression

Synthesis of siRNA nanoparticles to silence plaque-destabilizing gene in atherosclerotic lesional macrophages

FLEP-seq: simultaneous detection of RNA polymerase II position, splicing status, polyadenylation site and poly(A) tail length at genome-wide scale by single-molecule nascent RNA sequencing

Scalable tissue labeling and clearing of intact human organs

Analyzing somatic mutations by single-cell whole-genome sequencing

查看全部

Sections

Figures

References

Induced pluripotent stem cell-derived brain organoids enable the developmental complexities of the human brain to be deconstructed. During embryogenesis, optic vesicles (OVs), the eye primordium attached to the forebrain, develop from diencephalon. Howeve
Introduction
Materials
Procedure
Troubleshooting
Timing
Anticipated results
- References
References
ACKNOWLEDGMENTS

Mariani, J. & Vaccarino, F. M. Breakthrough moments: Yoshiki Sasai’s discoveries in the third dimension. Cell Stem Cell 24, 837–838 (2019).
Giandomenico, S. L., Sutcliffe, M. & Lancaster, M. A. Generation and long-term culture of advanced cerebral organoids for studying later stages of neural development. Nat. Protoc. 16, 579–602 (2021).
Bergmann, S. et al. Blood-brain-barrier organoids for investigating the permeability of CNS therapeutics. Nat. Protoc. 13, 2827–2843 (2018).
Gabriel, E. et al. CPAP promotes timely cilium disassembly to maintain neural progenitor pool. EMBO J. 35, 803–819 (2016).
Gabriel, E. et al. Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell 28, 1740–1757.e8 (2021).
Gopalakrishnan, J. The emergence of stem cell-based brain organoids: trends and challenges. BioEssays 41, e1900011 (2019).
Ramani, A. et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J. 39, e106230 (2020).
Sloan, S. A., Andersen, J., Pașca, A. M., Birey, F. & Pașca, S. P. Generation and assembly of human brain region-specific three-dimensional cultures. Nat. Protoc. 13, 2062–2085 (2018).
Quadrato, G. et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545, 48–53 (2017).
Goranci-Buzhala, G. et al. Rapid and efficient invasion assay of glioblastoma in human brain organoids. Cell Rep. 31, 107738 (2020).
Birey, F. et al. Assembly of functionally integrated human forebrain spheroids. Nature 545, 54–59 (2017).
Huschke, E. Uber einige streitpunkte aus der anatomie des auges [German]. Z. Opthalmol. 4, 273–295 (1835).
Pander, H. Beiträge zur Entwickelungsgeschichte des Hühnchens im Eye [German] (1817).
Adelmann, H. Marcello Malpighi and the Evolution of Embryology Vol. 3 (Cornell Univ. Press, 1966).
Zhong, X. et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat. Commun. 5, 4047 (2014).
Capowski, E. E. et al. Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines. Development 146, dev171686 (2019).
Nakano, T. et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10, 771–785 (2012).
Cowan, C. S. et al. Cell types of the human retina and its organoids at single-cell resolution. Cell 182, 1623–1640.e34 (2020).
Vergara, M. N. et al. Three-dimensional automated reporter quantification (3D-ARQ) technology enables quantitative screening in retinal organoids. Development 144, 3698–3705 (2017).
Meyer, J. S. et al. Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells 29, 1206–1218 (2011).
Eldred, K. C. et al. Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Science 362, eaau6348 (2018).
Eldred, K. C. & Reh, T. A. Human retinal model systems: strengths, weaknesses, and future directions. Dev. Biol. 480, 114–122 (2021).
Fligor, C. M. et al. Extension of retinofugal projections in an assembled model of human pluripotent stem cell-derived organoids. Stem Cell Rep. 16, 2228–2241 (2021).
Graw, J. Eye development. Curr. Top. Dev. Biol. 90, 343–386 (2010).
Rao, R. C., Stern, J. H. & Temple, S. The eyeball’s connected to the brain ball. Cell Stem Cell 28, 1675–1677 (2021).
Fuhrmann, S. Eye morphogenesis and patterning of the optic vesicle. Curr. Top. Dev. Biol. 93, 61–84 (2010).
Adler, R. & Canto-Soler, M. V. Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies. Dev. Biol. 305, 1–13 (2007).
Dupacova, N., Antosova, B., Paces, J. & Kozmik, Z. Meis homeobox genes control progenitor competence in the retina. Proc. Natl Acad. Sci. USA 118, e2013136118 (2021).
Mann, I. C. The Development of the Human Eye 1st edn (Univ. Press, 1928).
O’Rahilly, R. The early development of the eye in staged human embryos. Contrib. Embryol. 38, 1–42 (1966).
O’Rahilly, R. The prenatal development of the human eye. Exp. Eye Res. 21, 93–112 (1975).
Gabriel, E. & Gopalakrishnan, J. Generation of iPSC-derived human brain organoids to model early neurodevelopmental disorders. J. Vis. Exp. 14, 55372 (2017).
Gabriel, E. et al. Recent zika virus isolates induce premature differentiation of neural progenitors in human brain organoids. Cell. Stem Cell. 20, 397–406.e5 (2017).
Zhang, W. et al. Modeling microcephaly with cerebral organoids reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly in neural progenitors. Nat. Commun. 10, 2612 (2019).
Rosen, D. & Mahabadi, N. Embryology, Optic Cup (StatPearls Publishing LLC, updated 8 May 2022); https://www.ncbi.nlm.nih.gov/books/NBK545150/
Cvekl, A. & Wang, W. L. Retinoic acid signaling in mammalian eye development. Exp. Eye Res. 89, 280–291 (2009).
Janesick, A., Wu, S. C. & Blumberg, B. Retinoic acid signaling and neuronal differentiation. Cell. Mol. Life Sci. 72, 1559–1576 (2015).
Morizane, A., Doi, D., Kikuchi, T., Nishimura, K. & Takahashi, J. Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells. J. Neurosci. Res. 89, 117–126 (2011).
Jin, M., Yuan, Q., Li, S. & Travis, G. H. Role of LRAT on the retinoid isomerase activity and membrane association of Rpe65. J. Biol. Chem. 282, 20915–20924 (2007).
Hu, J. & Bok, D. The use of cultured human fetal retinal pigment epithelium in studies of the classical retinoid visual cycle and retinoid-based disease processes. Exp. Eye Res. 126, 46–50 (2014).
Francis, P. J. Genetics of inherited retinal disease. J. R. Soc. Med. 99, 189–191 (2006).
Takagi, S. et al. Evaluation of transplanted autologous induced pluripotent stem cell-derived retinal pigment epithelium in exudative age-related macular degeneration. Ophthalmol. Retin. 3, 850–859 (2019).
Dahl-Jensen, S. & Grapin-Botton, A. The physics of organoids: a biophysical approach to understanding organogenesis. Development 144, 946–951 (2017).
He, Z. et al. Lineage recording in human cerebral organoids. Nat. Methods 19, 90–99 (2022).
Hu, S. et al. Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells. JCI Insight 1, e85558 (2016).
Phetfong, J. et al. Cell type of origin influences iPSC generation and differentiation to cells of the hematoendothelial lineage. Cell Tissue Res. 365, 101–112 (2016).
Bardy, C. et al. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro. Proc. Natl Acad. Sci. USA 112, E2725–E2734 (2015).
Slembrouck-Brec, A. et al. Reprogramming of adult retinal Müller glial cells into human-induced pluripotent stem cells as an efficient source of retinal cells. Stem Cells Int. 2019, 7858796 (2019).
Karch, C. M. et al. A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies. Stem Cell Rep. 13, 939–955 (2019).
Baharvand, H., Salekdeh, G. H., Taei, A. & Mollamohammadi, S. An efficient and easy-to-use cryopreservation protocol for human ES and iPS cells. Nat. Protoc. 5, 588–594 (2010).
Rivera, T., Zhao, Y., Ni, Y. & Wang, J. Human-induced pluripotent stem cell culture methods under cGMP conditions. Curr. Protoc. Stem Cell Biol. 54, e117 (2020).
Klingberg, A. et al. Fully automated evaluation of total glomerular number and capillary tuft size in nephritic kidneys using lightsheet microscopy. J. Am. Soc. Nephrol. 28, 452–459 (2017).
Maiorano, N. A. & Hindges, R. Restricted perinatal retinal degeneration induces retina reshaping and correlated structural rearrangement of the retinotopic map. Nat. Commun. 4, 1938 (2013).
Crish, S. D., Sappington, R. M., Inman, D. M., Horner, P. J. & Calkins, D. J. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Proc. Natl Acad. Sci. USA 107, 5196–5201 (2010).
Foxton, R., Osborne, A., Martin, K. R., Ng, Y. S. & Shima, D. T. Distal retinal ganglion cell axon transport loss and activation of p38 MAPK stress pathway following VEGF-A antagonism. Cell Death Dis. 7, e2212 (2016).
Hou, M. et al. Age-related visual impairments and retinal ganglion cells axonal degeneration in a mouse model harboring OPTN (E50K) mutation. Cell Death Dis. 13, 362 (2022).
Stoeckel, K., Schwab, M. & Thoenen, H. Role of gangliosides in the uptake and retrograde axonal transport of cholera and tetanus toxin as compared to nerve growth factor and wheat germ agglutinin. Brain Res. 132, 273–285 (1977).
Conte, W. L., Kamishina, H. & Reep, R. L. Multiple neuroanatomical tract-tracing using fluorescent alexa fluor conjugates of cholera toxin subunit B in rats. Nat. Protoc. 4, 1157–1166 (2009).
Huberman, A. D., Dehay, C., Berland, M., Chalupa, L. M. & Kennedy, H. Early and rapid targeting of eye-specific axonal projections to the dorsal lateral geniculate nucleus in the fetal macaque. J. Neurosci. 25, 4014–4023 (2005).
Mikkelsen, J. D. Visualization of efferent retinal projections by immunohistochemical identification of cholera toxin subunit B. Brain Res. Bull. 28, 619–623 (1992).
Yao, F. et al. Did you choose appropriate tracer for retrograde tracing of retinal ganglion cells? The differences between cholera toxin subunit B and fluorogold. PLoS ONE 13, e0205133 (2018).
Chen, Y. et al. Cited2 is required for the proper formation of the hyaloid vasculature and for lens morphogenesis. Development 135, 2939–2948 (2008).
Eiraku, M. & Sasai, Y. Self-formation of layered neural structures in three-dimensional culture of ES cells. Curr. Opin. Neurobiol. 22, 768–777 (2012).
Parfitt, D. A. et al. Identification and correction of mechanisms underlying inherited blindness in human iPSC-derived optic cups. Cell Stem Cell 18, 769–781 (2016).
Susaimanickam, P. J. et al. Generating minicorneal organoids from human induced pluripotent stem cells. Development 144, 2338–2351 (2017).
Foster, J. W. et al. Cornea organoids from human induced pluripotent stem cells. Sci. Rep. 7, 41286 (2017).
Hallam, D. et al. Human-induced pluripotent stem cells generate light responsive retinal organoids with variable and nutrient-dependent efficiency. Stem Cells 36, 1535–1551 (2018).
Kim, S. et al. Generation, transcriptome profiling, and functional validation of cone-rich human retinal organoids. Proc. Natl Acad. Sci. USA 116, 10824–10833 (2019).
Zerti, D. et al. IGFBPs mediate IGF-1’s functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids. Stem Cells 39, 458–466 (2021).
Kuwahara, A. et al. Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat. Commun. 6, 6286 (2015).
Reichman, S. et al. Generation of storable retinal organoids and retinal pigmented epithelium from adherent human ips cells in xeno-free and feeder-free conditions. Stem Cells 35, 1176–1188 (2017).
Gagliardi, G. et al. Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids. Stem Cell Rep. 11, 665–680 (2018).
Sullivan-Brown, J., Bisher, M. E. & Burdine, R. D. Embedding, serial sectioning and staining of zebrafish embryos using JB-4 resin. Nat. Protoc. 6, 46–55 (2011).
Gu, L., Cong, J., Zhang, J., Tian, Y. Y. & Zhai, X. Y. A microwave antigen retrieval method using two heating steps for enhanced immunostaining on aldehyde-fixed paraffin-embedded tissue sections. Histochem. Cell Biol. 145, 675–680 (2016).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
Risso, D., Ngai, J., Speed, T. P. & Dudoit, S. Normalization of RNA-seq data using factor analysis of control genes or samples. Nat. Biotechnol. 32, 896–902 (2014).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Bodenhofer, U., Kothmeier, A. & Hochreiter, S. APCluster: an R package for affinity propagation clustering. Bioinformatics 27, 2463–2464 (2011).
Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).
Albanna, W. et al. Electroretinographic assessment of inner retinal signaling in the isolated and superfused murine retina. Curr. Eye Res. 42, 1518–1526 (2017).

Generation of iPSC-derived human forebrain organoids assembling bilateral eye primordia

Supplementary information

推荐阅读