Reliability of human cortical organoid generation
Open accessAbstract
The differentiation of pluripotent stem cells in three-dimensional cultures can recapitulate key aspects of brain development, but protocols are prone to variable results. Here we differentiated multiple human pluripotent stem cell lines for over 100 d using our previously developed approach to generate brain-region-specific organoids called cortical spheroids and, using several assays, found that spheroid generation was highly reliable and consistent. We anticipate the use of this approach for large-scale differentiation experiments and disease modeling.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Guided cortical organoid differentiation yields highly reproducible organoids compared with unguided organoid differentiation.
“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 [73]
A number of groups were able to generate spheroids in chip-based devices, but the spheroids lack spatial complexity and cell types compared to fully-developed organoids.
“A number of groups were able to generate spheroids in chip-based devices171–173, but the spheroids lack spatial complexity and cell types compared to fully-developed organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [173]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · see citing works
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179 · see citing works
Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. E., Li, C., & Rabinovic, A. (2007) · Biostatistics · doi:10.1093/biostatistics/kxj037 · Cited by 8,658 · see citing works
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 · see citing works
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 · see citing works
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Paşca, A. M., Sloan, S. A., Clarke, L. E., Tian, Y., Makinson, C. D., Huber, N., Kim, C. H., Park, J.-Y., O'Rourke, N. A., Nguyen, K. D., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3415 · Cited by 1,609 · see citing works
Self-citationAssembly of functionally integrated human forebrain spheroids
Birey, F., Andersen, J., Makinson, C. D., Islam, S., Wei, W., Huber, N., Fan, H. C., Metzler, K. R. C., Panagiotakos, G., Thom, N., et al. (2017) · Nature · doi:10.1038/nature22330 · Cited by 1,365 · see citing works
Self-citationCell diversity and network dynamics in photosensitive human brain organoids
Quadrato, G., Nguyen, T., Macosko, E. Z., Sherwood, J. L., Min Yang, S., Berger, D. R., Maria, N., Scholvin, J., Goldman, M., Kinney, J. P., et al. (2017) · Nature · doi:10.1038/nature22047 · Cited by 1,321 · see citing works
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders
Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.034 · Cited by 1,149 · see citing works
Human cerebral organoids recapitulate gene expression programs of fetal neocortex development
Camp, J. G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520760112 · Cited by 1,130 · see citing works
The use of brain organoids to investigate neural development and disease
Di Lullo, E., & Kriegstein, A. R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.107 · Cited by 788 · see citing works
Sloan, S. A., Darmanis, S., Huber, N., Khan, T. A., Birey, F., Caneda, C., Reimer, R., Quake, S. R., Barres, B. A., & Paşca, S. P. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.035 · Cited by 593 · see citing works
Self-citationUsing iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome
Paşca, S. P., Portmann, T., Voineagu, I., Yazawa, M., Shcheglovitov, A., Paşca, A. M., Cord, B., Palmer, T. D., Chikahisa, S., Nishino, S., et al. (2011) · Nature Medicine · doi:10.1038/nm.2576 · Cited by 585 · see citing works
Self-citationBershteyn, M., Nowakowski, T. J., Pollen, A. A., Di Lullo, E., Nene, A., Wynshaw-Boris, A., & Kriegstein, A. R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.12.007 · Cited by 566 · see citing works
The rise of three-dimensional human brain cultures
Pașca, S. P. (2018) · Nature · doi:10.1038/nature25032 · Cited by 509 · see citing works
Self-citationGeneration and assembly of human brain region-specific three-dimensional cultures
Sloan, S. A., Andersen, J., Pașca, A. M., Birey, F., & Pașca, S. P. (2018) · Nature Protocols · doi:10.1038/s41596-018-0032-7 · Cited by 490 · see citing works
Self-citationCombinatorial labeling of single cells for gene expression cytometry
Fan, H. C., Fu, G. K., & Fodor, S. P. A. (2015) · Science · doi:10.1126/science.1258367 · Cited by 455 · see citing works
Self-citationStem Cell Models of Human Brain Development
Kelava, I., & Lancaster, M. A. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.05.022 · Cited by 371 · see citing works
Genetically engineered human cortical spheroid models of tuberous sclerosis
Blair, J. D., Hockemeyer, D. F., & Bateup, H. S. (2018) · Nature Medicine · doi:10.1038/s41591-018-0139-y · Cited by 207 · see citing works
A Quantitative Framework to Evaluate Modeling of Cortical Development by Neural Stem Cells
Stein, J. L., de la Torre-Ubieta, L., Tian, Y., Parikshak, N. N., Hernández, I. A., Marchetto, M. C., Baker, D. K., Lu, D., Hinman, C. R., Lowe, J. K., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.035 · Cited by 201 · see citing works
Self-citationSwimming muscles power suction feeding in largemouth bass
Camp, A. L., Roberts, T. J., & Brainerd, E. L. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508055112 · Cited by 198 · see citing works
Romero, I. G., Pavlovic, B. J., Hernando-Herraez, I., Zhou, X., Ward, M. C., Banovich, N. E., Kagan, C. L., Burnett, J. E., Huang, C. H., Mitrano, A., et al. (2015) · eLife · doi:10.7554/elife.07103 · Cited by 194 · see citing works
Oldham, M. C., Langfelder, P., & Horvath, S. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-63 · Cited by 154 · see citing works
Feeder-free, Xeno-free Generation of Cortical Spheroids From Human Pluripotent Stem Cells
Pașca, S. P., Yoon, S., & Pașca, S. P. (2018) · Protocol Exchange · doi:10.1038/protex.2018.123 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Individual brain organoids reproducibly form cell diversity of the human cerebral cortex
Velasco, S., Kedaigle, A. J., Simmons, S. K., Nash, A., Rocha, M., Quadrato, G., Paulsen, B., Nguyen, L., Adiconis, X., Regev, A., et al. (2019) · Nature · doi:10.1038/s41586-019-1289-x · Cited by 1,094 · see citing works
Trujillo, C. A., Gao, R., Negraes, P. D., Gu, J., Buchanan, J., Preissl, S., Wang, A., Wu, W., Haddad, G. G., Chaim, I. A., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.08.002 · Cited by 974 · see citing works
Brain organoids: advances, applications and challenges
Qian, X., Song, H., & Ming, G.-L. (2019) · Development · doi:10.1242/dev.166074 · Cited by 724 · see citing works
Generation of Functional Human 3D Cortico-Motor Assembloids
Andersen, J., Revah, O., Miura, Y., Thom, N., Amin, N. D., Kelley, K. W., Singh, M., Chen, X., Thete, M. V., Walczak, E. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.11.017 · Cited by 593 · see citing works
Self-citationMaturation 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 · see citing works
Self-citationMiura, Y., Li, M.-Y., Birey, F., Ikeda, K., Revah, O., Thete, M. V., Park, J.-Y., Puno, A., Lee, S. H., Porteus, M. H., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-00763-w · Cited by 418 · see citing works
Self-citationEngineered materials for organoid systems
Kratochvil, M. J., Seymour, A. J., Li, T. L., Pașca, S. P., Kuo, C. J., & Heilshorn, S. C. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0129-9 · Cited by 413 · see citing works
Self-citationTowards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
Vascularized human cortical organoids (vOrganoids) model cortical development in vivo
Shi, Y., Sun, L., Liu, J., Zhong, S., Wang, M., Li, R., Li, P., Guo, L., Fang, A., Chen, R., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000705 · Cited by 401 · see citing works
Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures
Marton, R. M., Miura, Y., Sloan, S. A., Li, Q., Revah, O., Levy, R. J., Huguenard, J. R., & Pașca, S. P. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0316-9 · Cited by 362 · see citing works
Self-citationLong-term maturation of human cortical organoids matches key early postnatal transitions
Gordon, A., Yoon, S., Tran, S. S., Makinson, C. D., Park, J. Y., Andersen, J., Valencia, A. M., Horvath, S., Xiao, X. G., Huguenard, J. R., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00802-y · Cited by 352 · see citing works
Self-citationBrain organoids for the study of human neurobiology at the interface of in vitro and in vivo
Chiaradia, I., & Lancaster, M. A. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00730-3 · Cited by 343 · see citing works
Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites
Veenvliet, J. V., Bolondi, A., Kretzmer, H., Haut, L., Scholze‐Wittler, M., Schifferl, D., Koch, F., Guignard, L., Kumar, A. S., Pustet, M., et al. (2020) · Science · doi:10.1126/science.aba4937 · Cited by 318 · see citing works
Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity
Victor, M. B., Leary, N., Luna, X., Meharena, H. S., Scannail, A. N., Bozzelli, P. L., Samaan, G., Murdock, M. H., von Maydell, D., Effenberger, A. H., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.07.005 · Cited by 316 · see citing works
Human 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 303 · see citing works
Chromatin accessibility dynamics in a model of human forebrain development
Trevino, A. E., Sinnott-Armstrong, N., Andersen, J., Yoon, S.-J., Huber, N., Pritchard, J. K., Chang, H. Y., Greenleaf, W. J., & Pașca, S. P. (2020) · Science · doi:10.1126/science.aay1645 · Cited by 251 · see citing works
Self-citationUzquiano, 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 250 · see citing works
Marton, R. M., & Pașca, S. P. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.11.004 · Cited by 249 · see citing works
Self-citationGhatak, 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 · see citing works
Synthetic 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 238 · see citing works
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 233 · see citing works
Self-citationLi, 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 · see citing works
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 224 · see citing works
Bioengineering 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 · see citing works
Advancing Cell Therapy for Neurodegenerative Diseases
Temple, S. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.03.017 · Cited by 202 · see citing works
Modeling Sporadic Alzheimer's Disease in Human Brain Organoids under Serum Exposure
Chen, X., Sun, G., Tian, E., Zhang, M., Davtyan, H., Beach, T. G., Reiman, E. M., Blurton‐Jones, M., Holtzman, D. M., & Shi, Y. (2021) · Advanced Science · doi:10.1002/advs.202101462 · Cited by 200 · see citing works
Neuronal defects in a human cellular model of 22q11.2 deletion syndrome
Khan, T. A., Revah, O., Gordon, A., Yoon, S.-J., Krawisz, A. K., Goold, C., Sun, Y., Kim, C. H., Tian, Y., Li, M.-Y., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1043-9 · Cited by 186 · see citing works
Self-citationEngineering brain assembloids to interrogate human neural circuits
Miura, Y., Li, M.-Y., Revah, O., Yoon, S., Narazaki, G., & Pașca, S. P. (2022) · Nature Protocols · doi:10.1038/s41596-021-00632-z · Cited by 182 · see citing works
Self-citationSzebényi, K., Wenger, L. M. D., Sun, Y., Dunn, A. W., Limegrover, C. A., Gibbons, G. M., Conci, E., Paulsen, O., Mierau, S. B., Balmus, G., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00923-4 · Cited by 181 · see citing works
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 176 · see citing works
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 · see citing works
Human 3D cellular model of hypoxic brain injury of prematurity
Pașca, A. M., Park, J.-Y., Shin, H.-W., Qi, Q., Revah, O., Krasnoff, R., O’Hara, R., Willsey, A. J., Palmer, T. D., & Pașca, S. P. (2019) · Nature Medicine · doi:10.1038/s41591-019-0436-0 · Cited by 174 · see citing works
Self-citationA human tissue screen identifies a regulator of ER secretion as a brain-size determinant
Esk, C., Lindenhofer, D., Haendeler, S., Wester, R. A., Pflug, F., Schroeder, B., Bagley, J. A., Elling, U., Zuber, J., von Haeseler, A., et al. (2020) · Science · doi:10.1126/science.abb5390 · Cited by 170 · see citing works
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 169 · see citing works
Self-citationBrain 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 167 · see citing works
Yang, X., Forró, C., Li, T. L., Miura, Y., Zaluska, T. J., Tsai, C., Kanton, S., McQueen, J. P., Chen, X., Mollo, V., et al. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-02081-3 · Cited by 164 · see citing works
Self-citationFloch, 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 162 · see citing works
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 · see citing works
Mitochondrial STAT3 exacerbates LPS-induced sepsis by driving CPT1a-mediated fatty acid oxidation
Li, R., Li, X., Zhao, J., Meng, F., Yao, C., Bao, E.-S., Sun, N., Chen, X., Cheng, W., Hua, H. M., et al. (2021) · Theranostics · doi:10.7150/thno.63751 · Cited by 158 · see citing works
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 155 · see citing works
Birey, F., Li, M.-Y., Gordon, A., Thete, M. V., Valencia, A. M., Revah, O., Pașca, A. M., Geschwind, D. H., & Pașca, S. P. (2022) · Cell stem cell · doi:10.1016/j.stem.2021.11.011 · Cited by 155 · see citing works
Self-citationSpatially controlled construction of assembloids using bioprinting
Roth, J. G., Brunel, L. G., Huang, M. S., Liu, Y., Cai, B., Sinha, S., Yang, F., Pașca, S. P., Shin, S., & Heilshorn, S. C. (2023) · Nature Communications · doi:10.1038/s41467-023-40006-5 · Cited by 149 · see citing works
Self-citationAssembloid CRISPR screens reveal impact of disease genes in human neurodevelopment
Meng, X., Yao, D., Imaizumi, K., Chen, X., Kelley, K. W., Reis, N., Thete, M. V., McKinney, A. A., Kulkarni, S., Panagiotakos, G., et al. (2023) · Nature · doi:10.1038/s41586-023-06564-w · Cited by 145 · see citing works
Self-citationHuman assembloid model of the ascending neural sensory pathway
Kim, J., Imaizumi, K., Jurjuţ, O. F., Kelley, K. W., Wang, D., Thete, M. V., Hudáčová, Z., Amin, N. D., Levy, R. J., Scherrer, G., et al. (2025) · Nature · doi:10.1038/s41586-025-08808-3 · Cited by 144 · see citing works
Self-citationThree-dimensional modeling of human neurodegeneration: brain organoids coming of age
Grenier, K., Kao, J., & Diamandis, P. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0500-7 · Cited by 127 · see citing works
Advancing models of neural development with biomaterials
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 120 · see citing works
Self-citationdos Reis, R. S., Sant, S., Keeney, H., Wagner, M. C. E., & Ayyavoo, V. (2020) · Scientific Reports · doi:10.1038/s41598-020-72214-0 · Cited by 113 · see citing works
Modeling and Targeting Alzheimer’s Disease With Organoids
Papaspyropoulos, A., Tsolaki, M., Foroglou, N., & Pantazaki, Α. A. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00396 · Cited by 107 · see citing works
3D Brain Organoids: Studying Brain Development and Disease Outside the Embryo
Velasco, S., Paulsen, B. D. S., & Arlotta, P. (2020) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050154 · Cited by 107 · see citing works
Human 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 106 · see citing works
Primate cell fusion disentangles gene regulatory divergence in neurodevelopment
Agoglia, R. M., Sun, D., Birey, F., Yoon, S., Miura, Y., Sabatini, K., Pașca, S. P., & Fraser, H. B. (2021) · Nature · doi:10.1038/s41586-021-03343-3 · Cited by 102 · see citing works
Self-citationWang, 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 102 · see citing works
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 101 · see citing works
Controllable fusion of human brain organoids using acoustofluidics
Ao, Z., Cai, H., Wu, Z., Ott, J., Wang, H., Mackie, K., & Guo, F. (2021) · Lab on a Chip · doi:10.1039/d0lc01141j · Cited by 102 · see citing works
Qu, F., Brough, S. C., Michno, W., Madubata, C. J., Hartmann, G. G., Puno, A., Drainas, A. P., Bhattacharya, D., Tomasich, E., Lee, M. C., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01241-6 · Cited by 101 · see citing works
Self-citation3D Bioprinting using UNIversal Orthogonal Network (UNION) Bioinks
Hull, S. M., Lindsay, C. D., Brunel, L. G., Shiwarski, D. J., Tashman, J. W., Roth, J. G., Myung, D. J., Feinberg, A. W., & Heilshorn, S. C. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202007983 · Cited by 98 · see citing works
Cell diversity in the human cerebral cortex: from the embryo to brain organoids
Arlotta, P., & Pașca, S. P. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.03.001 · Cited by 96 · see citing works
Self-citationMartínez-Mármol, R., Giordano-Santini, R., Kaulich, E., Cho, A.-N., Przybyla, M., Riyadh, M. A., Robinson, E., Chew, K. Y., Amor, R., Meunier, F. A., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg2248 · Cited by 94 · see citing works
Papes, F., Camargo, A. P., de Souza, J. S., Carvalho, V. M. D. A., Szeto, R. A., LaMontagne, E., Júnior, J. R. T., Avansini, S. H., Sánchez-Sánchez, S. M., Nakahara, T. S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29942-w · Cited by 92 · see citing works
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 90 · see citing works
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 90 · see citing works
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 · see citing works
Microfluidics for Neuronal Cell and Circuit Engineering
Habibey, R., Arias, J. E. R., Striebel, J., & Busskamp, V. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00212 · Cited by 86 · see citing works
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 85 · see citing works
Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems
Silva-Pedrosa, R., Salgado, A. J., & Ferreira, P. E. (2023) · Cells · doi:10.3390/cells12060930 · Cited by 84 · see citing works
Middle-out methods for spatiotemporal tissue engineering of organoids
Blatchley, M. R., & Anseth, K. S. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00039-3 · Cited by 84 · see citing works
Aging, Cellular Senescence, and Progressive Multiple Sclerosis
Papadopoulos, D., Magliozzi, R., Mitsikostas, D. D., Gorgoulis, V. G., & Nicholas, R. S. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00178 · Cited by 83 · see citing works
Robust production of uniform human cerebral organoids from pluripotent stem cells
Sivitilli, A., Gosio, J., Ghoshal, B., Evstratova, A., Trcka, D., Ghiasi, P., Hernández, J. J., Beaulieu, J., Wrana, J. L., & Attisano, L. (2020) · Life Science Alliance · doi:10.26508/lsa.202000707 · Cited by 82 · see citing works
Fowler, J. L., Ang, L., & Loh, K. (2019) · Wiley Interdisciplinary Reviews: Developmental Biology · doi:10.1002/wdev.368 · Cited by 76 · see citing works
Generation of inner ear hair cells by direct lineage conversion of primary somatic cells
Menendez, L., Trecek, T., Gopalakrishnan, S., Tao, L., Markowitz, A. L., Yu, H. V., Wang, X., Llamas, J., Huang, C., Lee, J. D., et al. (2020) · eLife · doi:10.7554/elife.55249 · Cited by 80 · see citing works
Evolutionary conservation and divergence of the human brain transcriptome
Pembroke, W. G., Hartl, C., & Geschwind, D. H. (2021) · Genome biology · doi:10.1186/s13059-020-02257-z · Cited by 78 · see citing works
Self-citationChen, C., Rengarajan, V., Kjar, A., & Huang, Y. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.10.003 · Cited by 77 · see citing works
Understanding Immune‐Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform
Ao, Z., Song, S., Tian, C., Cai, H., Li, X., Miao, Y., Wu, Z., Krzesniak, J., Ning, B., Gu, M., et al. (2022) · Advanced Science · doi:10.1002/advs.202200475 · Cited by 77 · see citing works
Stretchable mesh microelectronics for the biointegration and stimulation of human neural organoids
Li, T. L., Liu, Y., Forró, C., Yang, X., Beker, L., Bao, Z., Cui, B., & Pașca, S. P. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121825 · Cited by 73 · see citing works
Self-citationCruceanu, C., Dony, L., Krontira, A. C., Fischer, D. S., Roeh, S., Giaimo, R. D., Kyrousi, C., Kaspar, L., Arloth, J., Czamara, D., et al. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2021.21010095 · Cited by 70 · see citing works
Generating human neural diversity with a multiplexed morphogen screen in organoids
Amin, N. D., Kelley, K. W., Kaganovsky, K., Onesto, M. M., Hao, J., Miura, Y., McQueen, J. P., Reis, N., Narazaki, G., Li, T., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.10.016 · Cited by 70 · see citing works
Self-citationThe Next 50 Years of Neuroscience
Altimus, C. M., Marlin, B. J., Charalambakis, N., Colón-Rodríguez, A., Glover, E. J., Izbicki, P., Johnson, A. C., Lourenco, M. V., Makinson, R. A., McQuail, J. A., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0744-19.2019 · Cited by 67 · see citing works
Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids
Tian, A., Muffat, J., & Li, Y. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0519-19.2019 · Cited by 67 · see citing works
Intracellular energy controls dynamics of stress-induced ribonucleoprotein granules
Wang, T., Tian, X., Kim, H. B., Jang, Y., Huang, Z., Na, C. H., & Wang, J. (2022) · Nature Communications · doi:10.1038/s41467-022-33079-1 · Cited by 67 · see citing works
Dissecting the complexities of Alzheimer disease with in vitro models of the human brain
Blanchard, J., Victor, M. B., & Tsai, L. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00578-6 · Cited by 65 · see citing works
Brain Organoids as Tools for Modeling Human Neurodevelopmental Disorders
Adams, J. W., Cugola, F. R., & Muotri, A. R. (2019) · Physiology · doi:10.1152/physiol.00005.2019 · Cited by 64 · see citing works
Sebastian, R., Jin, K., Pavon, N., Bansal, R., Potter, A., Song, Y., Babu, J., Gabriel, R., Sun, Y., Aronow, B. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39420-6 · Cited by 63 · see citing works
Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing
Yang, R., Feng, X., Arias‐Cavieres, A., Mitchell, R. M., Polo, A., Hu, K., Zhong, R., Qi, C., Zhang, R. S., Westneat, N., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.02.021 · Cited by 62 · see citing works
Proteostatic regulation in neuronal compartments
Giandomenico, S. L., Alvarez‐Castelao, B., & Schuman, E. M. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.08.002 · Cited by 61 · see citing works
Pushing the boundaries of brain organoids to study Alzheimer’s disease
Cerneckis, J., Bu, G., & Shi, Y. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.05.007 · Cited by 61 · see citing works
Park, Y., Chung, T. S., Lee, G., & Rogers, J. A. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00639 · Cited by 60 · see citing works
Martins‐Costa, C., Pham, V. A., Sidhaye, J., Novatchkova, M., Wiegers, A., Peer, A. M., Möseneder, P., Corsini, N. S., & Knoblich, J. A. (2023) · The EMBO Journal · doi:10.15252/embj.2022113213 · Cited by 59 · see citing works
Lai, J. D., Berlind, J. E., Fricklas, G., Lie, C., Urenda, J., Lam, K., Maria, N. S. S., Jacobs, R. E., Yu, V. L., Zhao, Z., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2024.03.004 · Cited by 58 · see citing works
How well do brain organoids capture your brain?
Kim, J., Sullivan, G. J., & Park, I. (2021) · iScience · doi:10.1016/j.isci.2021.102063 · Cited by 57 · see citing works
Dissecting Alzheimer's disease pathogenesis in human 2D and 3D models
Cenini, G., Hebisch, M., Iefremova, V., Flitsch, L. J., Breitkreuz, Y., Tanzi, R. E., Kim, D. Y., Peitz, M., & Brüstle, O. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103568 · Cited by 56 · see citing works
Brain Organoids as Model Systems for Genetic Neurodevelopmental Disorders
Baldassari, S., Musante, I., Iacomino, M., Zara, F., Salpietro, V., & Scudieri, P. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.590119 · Cited by 56 · see citing works
Modeling of Hypoxic Brain Injury through 3D Human Neural Organoids
Kim, M. S., Kim, D., Kang, H. K., Kook, M. G., Choi, S. W., & Kang, K. (2021) · Cells · doi:10.3390/cells10020234 · Cited by 55 · see citing works
Kim, E., Jeong, E., Hong, Y., Jeong, I., Kim, J.-H., Kwon, Y. W., Park, Y., Lee, J., Choi, S., Kim, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55752-3 · Cited by 56 · see citing works
Biomaterials and Culture Systems for Development of Organoid and Organ-on-a-Chip Models
D’Costa, K. A., Kosic, M., Lam, A., Moradipour, A., Zhao, Y., & Radisic, M. (2020) · Annals of Biomedical Engineering · doi:10.1007/s10439-020-02498-w · Cited by 54 · see citing works
Cerebral organoids as tools to identify the developmental roots of autism
Chan, W. K., Griffiths, R., Price, D. J., & Mason, J. O. (2020) · Molecular Autism · doi:10.1186/s13229-020-00360-3 · Cited by 54 · see citing works
Li, Z., Xu, J., Lang, Y., Fan, X., Kuo, L., D’Brant, L., Hu, S., Samrat, S. K., Trudeau, N., Tharappel, A. M., et al. (2020) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.0c00217 · Cited by 54 · see citing works
Strong, C. E., Zhang, J., Carrasco, M., Kundu, S., Boutin, M. E., Vishwasrao, H. D., Liu, J., Medina, A., Chen, Y., Wilson, K. M., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05582-8 · Cited by 52 · see citing works
Organoid assessment technologies
Gu, Y., Zhang, W. C., Wu, X., Zhang, Y., Xu, K., & Su, J. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1499 · Cited by 52 · see citing works
Ramani, A., Pasquini, G., Gerkau, N. J., Jadhav, V., Vinchure, O. S., Altinisik, N., Windoffer, H., Muller, S. M., Rothenaigner, I., Lin, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-55226-6 · Cited by 51 · see citing works
Porciúncula, L. O., Goto‐Silva, L., Ledur, P. F., & Rehen, S. K. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.674563 · Cited by 51 · see citing works
- Authors
- Yoon, S.-J., Elahi, L. S., Pașca, A. M., Marton, R. M., Gordon, A., Revah, O., Miura, Y., Walczak, E. M., Holdgate, G. M., Fan, H. C., Huguenard, J. R., Geschwind, D. H., & Pașca, S. P.
- Affiliations
- Stanford Medicine (US)
- University of California, Los Angeles (US)
- BD Biosciences (United States) (US)
- Corresponding author
- Pașca, Sergiu P.
- ORCID
- Venue
- Nature Methods
- Published
- 2018-12-20
- Volume
- 16
- Issue
- 1
- Pages
- 75-78
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC6677388
- OpenAlex
- W2904130550
- Cited by
- 507
- References
- 28
- Citations by year
- 2026: 66 · 2025: 74 · 2024: 57 · 2023: 59 · 2022: 67 · 2021: 70 · 2020: 76 · 2019: 35 · 2012: 1
- FWCI
- 16.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- New York Stem Cell Foundation
- Nature
- National Institutes of Health
- National Institute of Mental Health (R01MH107800, U01MH115745, U01MH115746)
- National Institute of Neurological Disorders and Stroke (R01NS034774)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD000850)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- cortical organoids, human pluripotent stem cells, brain development, xeno-free culture, feeder-free culture, disease modeling
- MeSH terms
- Cell Line, Humans, Organoids, Reproducibility of Results, Prosencephalon, Sequence Analysis, RNA, Tissue Engineering, Pluripotent Stem Cells, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review