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Individual brain organoids reproducibly form cell diversity of the human cerebral cortex
Open accessAbstract
Experimental models of the human brain are needed for basic understanding of its development and disease 1. Human brain organoids hold unprecedented promise for this purpose; however, they are plagued by high organoid-to-organoid variability 2,3. This has raised doubts as to whether developmental processes of the human brain can occur outside the context of embryogenesis with a degree of reproducibility that is comparable to the endogenous tissue. Here we show that an organoid model of the dorsal forebrain can reliably generate a rich diversity of cell types appropriate for the human cerebral cortex. We performed single-cell RNA-sequencing analysis of 166,242 cells isolated from 21 individual organoids, finding that 95% of the organoids generate a virtually indistinguishable compendium of cell types, following similar developmental trajectories and with a degree of organoid-to-organoid variability comparable to that of individual endogenous brains. Furthermore, organoids derived from different stem cell lines show consistent reproducibility in the cell types produced. The data demonstrate that reproducible development of the complex cellular diversity of the central nervous system does not require the context of the embryo, and that establishment of terminal cell identity is a highly constrained process that can emerge from diverse stem cell origins and growth environments.
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“Furthermore, several studies have shown that guided cortical organoid differentiation yields highly reproducible organoids as compared to unguided organoid differentiation (72–74).”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [74]
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“Organoid development followed the expected temporal changes (Lancaster et al., 2013; Velasco et al., 2019; Watanabe et al., 2017; Yoon et al., 2019; Figures 1B–1D; Figure S1A).”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Velasco et al., 2019
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“scRNA-seq analysis of human intestinal and brain organoids used random forest classifiers to identify the cell types in their organoid cultures;73,74”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [74]
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“All cell sub-types were present in WA25 and DSP-GFP organoids, but in different proportions (Fig. 2b, c), suggesting further protocol optimization may be needed to reduce variability19.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [19]
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Citations
Cites
Classification and Regression by randomForest
Liaw, A. I., & Wiener, M. C. (2007) · Cited by 18,594
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372
Reversed graph embedding resolves complex single-cell trajectories
Qiu, X., Mao, Q., Tang, Y., Wang, L., Chawla, R., Pliner, H. A., & Trapnell, C. (2017) · Nature Methods · doi:10.1038/nmeth.4402 · Cited by 5,070
Scrublet: computational identification of cell doublets in single-cell transcriptomic data
Wolock, S. L., Lopez, R., & Klein, A. M. (2018) · doi:10.1101/357368 · Cited by 2,758 · cited 1×
“1 39 was used to assess the effect of droplets that may have contained more than one cell, with an expected doublet rate of 0.1 and a score threshold of 0.39, chosen based on histograms of simulated doublet scores (Extended Data Fig.”
InfluentialScrublet: computational identification of cell doublets in single-cell transcriptomic data
Wolock, S. L., Lopez, R., & Klein, A. M. (2019) · Cell Systems · doi:10.1016/j.cels.2018.11.005 · Cited by 2,758
Zhang, Y., Sloan, S. A., Clarke, L. E., Caneda, C., Plaza, C. A., Blumenthal, P. D., Vogel, H., Steinberg, G. K., Edwards, M. S. B., Li, G., et al. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.013 · Cited by 2,295
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure
Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G. R., Jacob, F., Zhong, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.032 · Cited by 2,127
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
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Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song, E., Zhang, C., Israelow, B., Lu-Culligan, A., Prado, A. V., Skriabine, S., Lu, P., Weizman, O.-E., Liu, F., Dai, Y., et al. (2020) · doi:10.1101/2020.06.25.169946 · Cited by 1,064
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Kanton, S., Boyle, M. J., He, Z., Santel, M., Weigert, A., Sanchís-Calleja, F., Guijarro, P., Sidow, L., Fleck, J. S., Han, D., et al. (2019) · Nature · doi:10.1038/s41586-019-1654-9 · Cited by 778
Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution
Cowan, C. S., Renner, M., De Gennaro, M., Gross-Scherf, B., Goldblum, D., Hou, Y., Munz, M., Rodrigues, T. M., Krol, J., Szikra, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.013 · Cited by 654
Cell stress in cortical organoids impairs molecular subtype specification
Bhaduri, A., Andrews, M. G., Mancia Leon, W., Jung, D., Shin, D., Allen, D., Jung, D., Schmunk, G., Haeussler, M., Salma, J., et al. (2020) · Nature · doi:10.1038/s41586-020-1962-0 · Cited by 624
Maturation and circuit integration of transplanted human cortical organoids
Revah, O., Gore, F., Kelley, K. W., Andersen, J., Sakai, N., Chen, X., Li, M.-Y., Birey, F., Yang, X., Saw, N. L., et al. (2022) · Nature · doi:10.1038/s41586-022-05277-w · Cited by 504
Hair-bearing human skin generated entirely from pluripotent stem cells
Lee, J., Rabbani, C. C., Gao, H., Steinhart, M. R., Woodruff, B. M., Pflum, Z. E., Kim, A., Heller, S., Liu, Y., Shipchandler, T. Z., et al. (2020) · Nature · doi:10.1038/s41586-020-2352-3 · Cited by 487
Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation
Qian, X., Su, Y., Adam, C. D., Deutschmann, A. U., Pather, S. R., Goldberg, E. M., Su, K., Li, S., Lu, L., Jacob, F., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.02.002 · Cited by 479
Autism genes converge on asynchronous development of shared neuron classes
Paulsen, B., Velasco, S., Kedaigle, A. J., Pigoni, M., Quadrato, G., Deo, A. J., Adiconis, X., Uzquiano, A., Sartore, R., Yang, S. M., et al. (2022) · Nature · doi:10.1038/s41586-021-04358-6 · Cited by 439
Self-citationKatsura, H., Sontake, V., Tata, A., Kobayashi, Y., Edwards, C. E., Heaton, B. E., Konkimalla, A., Asakura, T., Mikami, Y., Fritch, E. J., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.10.005 · Cited by 416
Single cell transcriptomics comes of age
Aldridge, S., & Teichmann, S. A. (2020) · Nature Communications · doi:10.1038/s41467-020-18158-5 · Cited by 360
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Chiaradia, I., & Lancaster, M. A. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00730-3 · Cited by 360
In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes
Jin, X., Simmons, S. K., Guo, A., Shetty, A. S., Ko, M., Nguyen, L., Jokhi, V., Robinson, E., Oyler, P., Curry, N., et al. (2020) · Science · doi:10.1126/science.aaz6063 · Cited by 317
Self-citationHuman cerebral organoids — a new tool for clinical neurology research
Eichmüller, O. L., & Knoblich, J. A. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00723-9 · Cited by 319
Giandomenico, S. L., Sutcliffe, M. A., & Lancaster, M. A. (2020) · Nature Protocols · doi:10.1038/s41596-020-00433-w · Cited by 293
BANKSY unifies cell typing and tissue domain segmentation for scalable spatial omics data analysis
Singhal, V., Chou, N., Lee, J., Yue, Y., Liu, J., Chock, W. K., Lin, L., Chang, Y.-C., Teo, E. M. L., Aow, J., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01664-3 · Cited by 282
Modeling neoplastic disease with spheroids and organoids
Zanoni, M., Cortesi, M., Zamagni, A., Arienti, C., Pignatta, S., & Tesei, A. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00931-0 · Cited by 280
Cheroni, C., Caporale, N., & Testa, G. (2020) · Molecular Autism · doi:10.1186/s13229-020-00370-1 · Cited by 290
Single-Cell RNA Sequencing Analysis: A Step-by-Step Overview
Slovin, S., Carissimo, A., Panariello, F., Grimaldi, A., Bouchè, V., Gambardella, G., & Cacchiarelli, D. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1307-8_19 · Cited by 264
Challenges of Organoid Research
Andrews, M. G., & Kriegstein, A. R. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-111020-090812 · Cited by 270
Uzquiano, A., Kedaigle, A. J., Pigoni, M., Paulsen, B. D. S., Adiconis, X., Kim, K., Faits, T., Nagaraja, S., Antón-Bolaños, N., Gerhardinger, C., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.010 · Cited by 257
Self-citationSynthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain
Tanaka, Y., Çakır, B., Xiang, Y., Sullivan, G. J., & Park, I. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.038 · Cited by 244
A connectomic study of a petascale fragment of human cerebral cortex
Shapson-Coe, A., Januszewski, M., Berger, D. R., Pope, A., Wu, Y., Blakely, T., Schalek, R. L., Li, P. H., Wang, S., Maitin-Shepard, J., et al. (2021) · doi:10.1101/2021.05.29.446289 · Cited by 243
Human brain organogenesis: Toward a cellular understanding of development and disease
Kelley, K. W., & Pașca, S. P. (2021) · Cell · doi:10.1016/j.cell.2021.10.003 · Cited by 244
Ghatak, S., Dolatabadi, N., Trudler, D., Zhang, X., Wu, Y., Mohata, M., Ambasudhan, R., Talantova, M., & Lipton, S. A. (2019) · eLife · doi:10.7554/elife.50333 · Cited by 227
Li, Q., Nan, K., Le Floch, P., Lin, Z., Sheng, H., Blum, T. S., & Liu, J. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b02512 · Cited by 224
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Rood, J. E., Maartens, A., Hupalowska, A., Teichmann, S. A., & Regev, A. (2022) · Nature Medicine · doi:10.1038/s41591-022-02104-7 · Cited by 222
Self-citationBioengineering Approaches for the Advanced Organoid Research
Yi, S. A., Zhang, Y., Rathnam, C., Pongkulapa, T., & Lee, K. (2021) · Advanced Materials · doi:10.1002/adma.202007949 · Cited by 218
Park, J., Jang, S., Lee, D., Lee, J.-H., Kang, U., Chang, H., Kim, H. J., Han, S.-H., Seo, J., Choi, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20440-5 · Cited by 227
Lineage recording in human cerebral organoids
He, Z., Maynard, A., Jain, A., Gerber, T., Petri, R., Lin, H., Santel, M., Ly, K. C. H., Dupré, J.-S., Sidow, L., et al. (2021) · Nature Methods · doi:10.1038/s41592-021-01344-8 · Cited by 204
A Droplet Microfluidic System to Fabricate Hybrid Capsules Enabling Stem Cell Organoid Engineering
Liu, H., Wang, Y., Wang, H., Zhao, M., Tao, T., Zhang, X., & Qin, J. (2020) · Advanced Science · doi:10.1002/advs.201903739 · Cited by 194
Galan, E. A., Zhao, H., Wang, X., Dai, Q., Huck, W. T. S., & Ma, S. (2020) · Matter · doi:10.1016/j.matt.2020.08.034 · Cited by 194
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Jiang, S., Zhao, H., Zhang, W., Wang, J., Liu, Y., Cao, Y., Zheng, H., Hu, Z., Wang, S., Zhu, Y., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100161 · Cited by 188
Microglia-containing human brain organoids for the study of brain development and pathology
Zhang, W., Jiang, J., Xu, Z., Yan, H., Tang, B., Liu, C., Chen, C., & Meng, Q. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01892-1 · Cited by 195
Applications of organoids for cancer biology and precision medicine
Lo, Y.-H., Karlsson, K., & Kuo, C. J. (2020) · Nature Cancer · doi:10.1038/s43018-020-0102-y · Cited by 182
Bowles, K. R., Silva, M. C., Whitney, K., Bertucci, T., Berlind, J. E., Lai, J. D., Garza, J. C., Boles, N. C., Mahali, S., Strang, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.003 · Cited by 175
Production of human spinal-cord organoids recapitulating neural-tube morphogenesis
Lee, J., Shin, H., Shaker, M. R., Kim, H. J., Park, S.-H., Kim, J. H., Lee, N., Kang, M., Cho, S., Kwak, T. H., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00868-4 · Cited by 179
Human organoids: New strategies and methods for analyzing human development and disease
Corsini, N. S., & Knoblich, J. A. (2022) · Cell · doi:10.1016/j.cell.2022.06.051 · Cited by 176
Brain organoids: an ensemble of bioassays to investigate human neurodevelopment and disease
Sidhaye, J., & Knoblich, J. A. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0566-4 · Cited by 170
Amplification of human interneuron progenitors promotes brain tumors and neurological defects
Eichmüller, O. L., Corsini, N. S., Vértesy, Á., Morassut, I., Scholl, T., Gruber, V.-E., Peer, A. M., Chu, J., Novatchkova, M., Hainfellner, J. A., et al. (2022) · Science · doi:10.1126/science.abf5546 · Cited by 163
Floch, P. L., Li, Q., Lin, Z., Zhao, S., Liu, R., Tasnim, K., Jiang, H., & Jia Liu, B. (2022) · Advanced Materials · doi:10.1002/adma.202106829 · Cited by 166
Dao, L., You, Z., Lu, L., Xu, T., Sarkar, A. K., Zhu, H., Liu, M., Calandrelli, R., Yoshida, G., Lin, P., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.04.019 · Cited by 181
Qu, J., Kalyani, F. S., Liu, L., Cheng, T., & Chen, L. (2021) · 癌症：英文版 · doi:10.1002/cac2.12224 · Cited by 173
Skylar-Scott, M. A., Huang, J. Y., Lu, A., Ng, A. H. M., Duenki, T., Liu, S., Nam, L. L., Damaraju, S., Church, G. M., & Lewis, J. A. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00856-8 · Cited by 160
Cakir, B., Tanaka, Y., Kiral, F. R., Xiang, Y., Dagliyan, O., Wang, J., Lee, M., Greaney, A. M., Yang, W. S., duBoulay, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28043-y · Cited by 162
An integrated transcriptomic cell atlas of human neural organoids
He, Z., Dony, L., Fleck, J. S., Szałata, A., Li, K. X., Slišković, I., Lin, H., Santel, M., Atamian, A., Quadrato, G., et al. (2024) · Nature · doi:10.1038/s41586-024-08172-8 · Cited by 190
Self-citationOne-Stop Microfluidic Assembly of Human Brain Organoids To Model Prenatal Cannabis Exposure
Ao, Z., Cai, H., Havert, D., Wu, Z., Gong, Z., Beggs, J. M., Mackie, K., & Guo, F. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c00205 · Cited by 162
Fiorenzano, A., Sozzi, E., Birtele, M., Kajtez, J., Giacomoni, J., Nilsson, F., Bruzelius, A., Sharma, Y., Zhang, Y., Mattsson, B., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27464-5 · Cited by 160
Hua, T., Kiran, S., Li, Y., & Sang, Q. A. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2022.128884 · Cited by 163
Pereira, J. D., DuBreuil, D. M., Devlin, A., Held, A., Sapir, Y., Berezovski, E., Hawrot, J., Dorfman, K., Chander, V., & Wainger, B. J. (2021) · Nature Communications · doi:10.1038/s41467-021-24776-4 · Cited by 159
Making neurons, made easy: The use of Neurogenin-2 in neuronal differentiation
Hulme, A. E., Maksour, S., Clair‐Glover, M. S., Miellet, S., & Dottori, M. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.11.015 · Cited by 153
Notaras, M., Lodhi, A., Dündar, F., Collier, P., Sayles, N. M., Tilgner, H., Greening, D., & Colak, D. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01316-6 · Cited by 150
Andrews, M. G., Subramanian, L., & Kriegstein, A. R. (2020) · eLife · doi:10.7554/elife.58737 · Cited by 148
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Birtele, M., Lancaster, M. A., & Quadrato, G. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00804-1 · Cited by 177
Self-citationHuman iPSC‐derived microglia: A growing toolset to study the brain's innate immune cells
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Wang, Y., & Jeon, H. (2022) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2022.03.014 · Cited by 143
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Urresti, J., Zhang, P., Losada, P. M., Yu, N., Negraes, P. D., Trujillo, C. A., Antaki, D., Amar, M., Chau, K. K., Pramod, A. B., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01243-6 · Cited by 135
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Liu, S. J., Malatesta, M., Lien, B. V., Saha, P., Thombare, S. S., Hong, S. J., Pedraza, L., Koontz, M., Seo, K., Horlbeck, M. A., et al. (2020) · Genome biology · doi:10.1186/s13059-020-01995-4 · Cited by 144
Human organoids-on-chips for biomedical research and applications
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Dehorter, N., & del Pino, I. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00283 · Cited by 143
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Poirier, E. Z., Buck, M. D., Chakravarty, P., Carvalho, J., Frederico, B., Cardoso, A., Healy, L. E., Ulferts, R., Beale, R. C. L., & Sousa, C. R. E. (2021) · Science · doi:10.1126/science.abg2264 · Cited by 133
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Fonseca, A. C., Melchels, F. P. W., Ferreira, M. J. S., Moxon, S. R., Potjewyd, G., Dargaville, T. R., Kimber, S. J., & Domingos, M. A. N. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00342 · Cited by 135
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Rauth, S., Karmakar, S., Batra, S. K., & Ponnusamy, M. P. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188527 · Cited by 135
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Klingler, E., Francis, F., Jabaudon, D., & Cappello, S. (2021) · Science · doi:10.1126/science.aba4517 · Cited by 131
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Xue, X., Kim, Y. S., Ponce, I., O’Laughlin, R., Yan, R. Z., Kobayashi, N., Tshuva, R. Y., Tsai, Y.-H., Sun, S., Zheng, Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07204-7 · Cited by 123
Transplantation of Human Brain Organoids: Revisiting the Science and Ethics of Brain Chimeras
Chen, H. I., Wolf, J. A., Blue, R., Song, M. M., Moreno, J. D., Ming, G., & Song, H. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.09.002 · Cited by 131
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Roth, J. G., Huang, M. S., Li, T. L., Feig, V. R., Jiang, Y., Cui, B., Greely, H. T., Bao, Z., Pașca, S. P., & Heilshorn, S. C. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00496-y · Cited by 122
de Jong, J. O., Llapashtica, C., Genestine, M., Strauss, K. A., Provenzano, F. A., Sun, Y., Zhu, H., Cortese, G. P., Brundu, F. G., Brigatti, K. W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24358-4 · Cited by 130
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Wells, M. F., Nemesh, J., Ghosh, S., Mitchell, J. M., Salick, M. R., Mello, C. J., Meyer, D., Pietilainen, O., Piccioni, F., Guss, E. J., et al. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.01.010 · Cited by 116
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Self-citationHuman fetal brain self-organizes into long-term expanding organoids
Hendriks, D. F. G., Pagliaro, A., Andreatta, F., Ma, Z., van Giessen, J., Massalini, S., López‐Iglesias, C., van Son, G. J. F., DeMartino, J., Damen, M. J. A., et al. (2024) · Cell · doi:10.1016/j.cell.2023.12.012 · Cited by 108
Brain Chimeroids reveal individual susceptibility to neurotoxic triggers
Antón-Bolaños, N., Faravelli, I., Faits, T., Andreadis, S., Kästli, R., Trattaro, S., Adiconis, X., Wei, A., Kumar, A. S., Bella, D. J. D., et al. (2024) · Nature · doi:10.1038/s41586-024-07578-8 · Cited by 115
Self-citationFOXP transcription factors in vertebrate brain development, function, and disorders
Co, M., Anderson, A. G., & Konopka, G. (2020) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.375 · Cited by 105
Upgrading the Physiological Relevance of Human Brain Organoids
Dosso, A. D., Urenda, J., Nguyen, T. N., & Quadrato, G. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.029 · Cited by 106
Self-citationTissue morphology influences the temporal program of human brain organoid development
Chiaradia, I., Imaz-Rosshandler, I., Nilges, B. S., Boulanger, J., Pellegrini, L., Das, R., Kashikar, N. D., & Lancaster, M. A. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.09.003 · Cited by 106
Chamling, X., Kallman, A., Fang, W., Berlinicke, C. A., Mertz, J. L., Devkota, P., Pantoja, I. E. M., Smith, M. D., Ji, Z., Chang, C. K. W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-20892-3 · Cited by 103
Applications of brain organoids in neurodevelopment and neurological diseases
Sun, N., Meng, X., Liu, Y., Song, D., Jiang, C., & Cai, J. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00728-4 · Cited by 103
Nicheformer: a foundation model for single-cell and spatial omics
Tejada-Lapuerta, A., Schaar, A. C., Gutgesell, R., Palla, G., Halle, L., Minaeva, M., Vornholz, L., Dony, L., Drummer, F., Richter, T., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02814-z · Cited by 100
Advanced 3D imaging and organoid bioprinting for biomedical research and therapeutic applications
Maharjan, S., Ma, C., Singh, B., Kang, H., Orive, G., Yao, J., & Zhang, Y. S. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115237 · Cited by 107
Organoids in image-based phenotypic chemical screens
Lukonin, I., Zinner, M., & Liberali, P. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00641-8 · Cited by 99
Wang, Y., Chiola, S., Yang, G., Russell, C., Armstrong, C. J., Wu, Y., Spampanato, J. G., Tarboton, P., Ullah, H. M. A., Edgar, N. U., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33364-z · Cited by 104
Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research
Düzağaç, F., Saorin, G., Memeo, L., Canzonieri, V., & Rizzolio, F. (2021) · Cancers · doi:10.3390/cancers13040737 · Cited by 97
Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids
Rybak‐Wolf, A., Wyler, E., Pentimalli, T. M., Legnini, I., Oliveras, A., Glažar, P., Loewa, A., Kim, S. J., Kaufer, B. B., Woehler, A., et al. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01405-y · Cited by 100
Yao, Q., Cheng, S., Pan, Q., Yu, J., Cao, G., Li, L., & Cao, H. (2024) · MedComm · doi:10.1002/mco2.735 · Cited by 100
Vanslambrouck, J. M., Wilson, S. B., Tan, K. S., Groenewegen, E., Rudraraju, R., Neil, J. A., Lawlor, K. T., Mah, S., Scurr, M., Howden, S. E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33623-z · Cited by 100
Human cerebral organoids and consciousness: a double-edged sword
Lavazza, A. (2020) · Bioethics News · doi:10.1007/s40592-020-00116-y · Cited by 96
Aguado, J., Chaggar, H. K., Gómez‐Inclán, C., Shaker, M. R., Leeson, H. C., Mackay‐Sim, A., & Wolvetang, E. J. (2021) · Aging Cell · doi:10.1111/acel.13468 · Cited by 92
Multiscale 3D phenotyping of human cerebral organoids
Albanese, A., Swaney, J., Yun, D. H., Evans, N. B., Antonucci, J. M., Velasco, S., Sohn, C. H., Arlotta, P., Gehrke, L., & Chung, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-78130-7 · Cited by 92
Self-citation3d organ-on-a-chip: the convergence of microphysiological systems and organoids
Baptista, L. S., Porrini, C., Kronemberger, G. S., Kelly, D. J., & Perrault, C. M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1043117 · Cited by 90
“, 2019) with a correlation of genetic variability according to donor cells (Velasco et al., 2019).”
BackgroundHuman Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities
Nascimento, J. M., Saia-Cereda, V. M., Sartore, R., da Costa, R. M., Schitine, C., Freitas, H. R., Murgu, M., Reis, R. A. D. M., Rehen, S. K., & Martins‐de‐Souza, D. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00303 · Cited by 92
Past, Present, and Future of Brain Organoid Technology.
Koo, B., Choi, B., Park, H., & Yoon, K. (2019) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2019.0162 · Cited by 93
Salaris, F., & Rosa, A. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146393 · Cited by 88
Rosebrock, D., Arora, S., Mutukula, N., Volkman, R., Gralinska, E., Balaskas, A., Aragonés Hernández, A., Buschow, R., Brändl, B., Müller, F.-J., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00929-5 · Cited by 89
Birtele, M., Dosso, A. D., Xu, T., Nguyen, T. N., Wilkinson, B., Hosseini, N., Nguyen, S. C., Urenda, J., Knight, G. T., Rojas, C., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01477-3 · Cited by 101
Self-citationLi, Q. (2023) · Genome biology · doi:10.1186/s13059-023-02988-9 · Cited by 103
Mapping human cell phenotypes to genotypes with single-cell genomics
Camp, J. G., Platt, R. J., & Treutlein, B. (2019) · Science · doi:10.1126/science.aax6648 · Cited by 85
Innovations in 3D Tissue Models of Human Brain Physiology and Diseases
Lovett, M. L., Nieland, T. J. F., Dingle, Y. L., & Kaplan, D. L. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909146 · Cited by 87
Metadata
- Authors
- Velasco, S., Kedaigle, A. J., Simmons, S. K., Nash, A., Rocha, M., Quadrato, G., Paulsen, B., Nguyen, L., Adiconis, X., Regev, A., Levin, J. Z., & Arlotta, P.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Arlotta, Paola
- ORCID
- Venue
- Nature
- Published
- 2019-06
- Volume
- 570
- Issue
- 7762
- Pages
- 523-527
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6906116
- OpenAlex
- W2949020598
- Cited by
- 1,094
- References
- 39
- Citations by year
- 2026: 145 · 2025: 156 · 2024: 184 · 2023: 131 · 2022: 148 · 2021: 142 · 2020: 150 · 2019: 35
- FWCI
- 44.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Broad Institute
- Stanley Center for Psychiatric Research, Broad Institute
- Klarman Cell Observatory, Broad Institute
- National Institute of Mental Health (P50MH094271, U01MH115727, R01MH112940)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- human brain organoids, cortical development, cell type diversity, dorsal forebrain, stem cell origin, reproducibility, single-cell transcriptomics
- MeSH terms
- RNA-Seq, Cell Line, Cerebral Cortex, Female, Fetus, Humans, Male, Organoids, Time Factors, Reproducibility of Results, Prosencephalon, Tissue Culture Techniques, Induced Pluripotent Stem Cells, Single-Cell Analysis, Transcriptome
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