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DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome
Open accessAbstract
Down syndrome (DS), caused by trisomy of chromosome 21, occurs in 1 of every 800 live births. Early defects in cortical development likely account for the cognitive impairments in DS, although the underlying molecular mechanism remains elusive. Here, we performed histological assays and unbiased single-cell RNA-Seq (scRNA-Seq) analysis on cerebral organoids derived from 4 euploid cell lines and from induced pluripotent stem cells (iPSCs) from 3 individuals with trisomy 21 to explore cell-type-specific abnormalities associated with DS during early brain development. We found that neurogenesis was significantly affected, given the diminished proliferation and decreased expression of layer II and IV markers in cortical neurons in the subcortical regions; this may have been responsible for the reduced size of the organoids. Furthermore, suppression of the DSCAM/PAK1 pathway, which showed enhanced activity in DS, using CRISPR/Cas9, CRISPR interference (CRISPRi), or small-molecule inhibitor treatment reversed abnormal neurogenesis, thereby increasing the size of organoids derived from DS iPSCs. Our study demonstrates that 3D cortical organoids developed in vitro are a valuable model of DS and provide a direct link between dysregulation of the DSCAM/PAK1 pathway and developmental brain defects in DS.
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“However, results from these studies are discordant: the generation of neurons from iPSCs has been reported in some studies to be impaired74,77–79 and in others not to be impaired75,80,81, which may be explained by technical differences in the cell lines and protocols used (see Box 1).”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [77]
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“Genome-wide dysregulation of gene expression (Box 3) in neurons likely leads to over-expression and/or under-expression of key genes that regulate synaptogenesis, but specific candidates have yet to be identified74,77,81,143.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [77]
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“Analyses of NPCs arising from T21 iPSCs have provided conflicting data, with some suggesting that apoptosis is increased74,79,95 and others seeing no effect75,77,81,96.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [77]
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Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype
Kim, D., Paggi, J. M., Park, C., Bennett, C., & Salzberg, S. L. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0201-4 · Cited by 15,022
Comprehensive integration of single-cell dataPreprint
Stuart, T., Butler, A. W., Hoffman, P. J., Hafemeister, C., Papalexi, E., Mauck, W., Hao, Y.-H., Stoeckius, M., Smibert, P., & Satija, R. (2018) · bioRxiv · doi:10.1101/460147 · Cited by 13,858
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
Hafemeister, C., & Satija, R. (2019) · Genome Biology · doi:10.1186/s13059-019-1874-1 · Cited by 4,479 · cited 1×
“SCTransform normalization was applied to each Seurat object to control confounding sources of variations such as sequencing depth and mitochondrial fraction (58).”
MethodFinak, G., McDavid, A., Yajima, M., Deng, J., Gersuk, V., Shalek, A. K., Slichter, C. K., Miller, H. W., McElrath, M. J., Prlic, M., et al. (2015) · Genome Biology · doi:10.1186/s13059-015-0844-5 · Cited by 3,159
Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics
Street, K., Risso, D., Fletcher, R. B., Das, D., Ngai, J., Yosef, N., Purdom, E., & Dudoit, S. (2018) · BMC Genomics · doi:10.1186/s12864-018-4772-0 · Cited by 3,159
ToppGene Suite for gene list enrichment analysis and candidate gene prioritization
Chen, J., Bardes, E. E., Aronow, B. J., & Jegga, A. G. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp427 · Cited by 2,952
Spatio-temporal transcriptome of the human brain
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., et al. (2011) · Nature · doi:10.1038/nature10523 · Cited by 2,084
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2Preprint
Love, M. I., Huber, W. K., & Anders, S. (2014) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/002832 · Cited by 1,849
Generation of cerebral organoids from human pluripotent stem cells
Lancaster, M. A., & Knoblich, J. A. (2014) · Nature Protocols · doi:10.1038/nprot.2014.158 · Cited by 1,823
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
Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M., & Sasai, Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315710110 · Cited by 999
Bershteyn, 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
Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model
Caviness, V. S., Takahashi, T., & Nowakowski, R. S. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)93933-o · Cited by 566
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
Miura, 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 431
Watanabe, M., Buth, J. E., Vishlaghi, N., de la Torre-Ubieta, L., Taxidis, J., Khakh, B. S., Coppola, G., Pearson, C. A., Yamauchi, K., Gong, D., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.047 · Cited by 401
Korbel, J. O., Tirosh-Wagner, T., Urban, A. E., Chen, X.-N., Kasowski, M., Dai, L., Grubert, F., Erdman, C., Gao, M. C., Lange, K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813248106 · Cited by 399
Lyle, R., Béna, F., Gagos, S., Gehrig, C., Lopez, G., Schinzel, A., Lespinasse, J., Bottani, A., Dahoun, S., Taine, L., et al. (2009) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.214 · Cited by 331
Building Models of Brain Disorders with Three-Dimensional Organoids
Amin, N. D., & Paşca, S. P. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.007 · Cited by 312
Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells
Liu, Y., Liu, H., Sauvey, C., Yao, L., Żarnowska, E. D., & Zhang, S. (2013) · Nature Protocols · doi:10.1038/nprot.2013.106 · Cited by 308
Self-citationWisniewski, K. E. (2005) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320370755 · Cited by 297
Yamakawa, K. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.2.227 · Cited by 292
Slingshot: Cell lineage and pseudotime inference for single-cell transcriptomicsPreprint
Street, K., Risso, D., Fletcher, R. B., Das, D., Ngai, J., Yosef, N., Purdom, E. A., & Dudoit, S. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/128843 · Cited by 290
Liu, Y., Weick, J. P., Liu, H., Krencik, R., Zhang, X., Ma, L., Zhou, G., Ayala, M., & Zhang, S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2565 · Cited by 279
Self-citationIefremova, V., Manikakis, G., Krefft, O., Jabali, A., Weynans, K., Wilkens, R., Marsoner, F., Brändl, B., Müller, F.-J., Koch, P., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.047 · Cited by 261
Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486
Dolan, B. M., Duron, S. G., Campbell, D. A., Vollrath, B., Rao, B. S. S., Ko, H.-Y., Lin, G. G., Govindarajan, A., Choi, S.-Y., & Tonegawa, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219383110 · Cited by 260
The neurobiologie consequences of down syndrome
Coyle, J. T., Oster-Granite, M. L., & Gearhart, J. D. (1986) · Brain Research Bulletin · doi:10.1016/0361-9230(86)90074-2 · Cited by 248
Hafemeister, C., & Satija, R. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/576827 · Cited by 238
Bahn, S., Mimmack, M., Ryan, M., Caldwell, M. A., Jauniaux, E., Starkey, M., Svendsen, C. N., & Emson, P. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07497-4 · Cited by 211
Development of the superior temporal neocortex is anomalous in trisomy 21
Golden, J. A., & Hyman, B. T. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00011 · Cited by 210
Chen, B. E., Kondo, M., Garnier, A., Watson, F. L., Püettmann-Holgado, R., Lamar, D. R., & Schmucker, D. (2006) · Cell · doi:10.1016/j.cell.2006.03.034 · Cited by 209
Assembling human brain organoids
Paşca, S. P. (2019) · Science · doi:10.1126/science.aau5729 · Cited by 208
Yoon, K., Song, G., Qian, X., Pan, J., Xu, D., Rho, H.-S., Kim, N.-S., Habela, C. W., Zheng, L., Jacob, F., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.014 · Cited by 206
Deficits in human trisomy 21 iPSCs and neurons
Weick, J. P., Held, D. L., Bonadurer, G. F., Doers, M. E., Liu, Y., Maguire, C., Clark, A., Knackert, J. A., Molinarolo, K., Musser, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216575110 · Cited by 205
Self-citationChakrabarti, L., Galdzicki, Z., & Haydar, T. F. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3406-07.2007 · Cited by 199
Xu, R., Brawner, A. T., Li, S., Liu, J.-J., Kim, H., Xue, H., Pang, Z. P., Kim, W.-Y., Hart, R. P., Liu, Y., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.04.014 · Cited by 193
Self-citationDown's syndrome: Is there a decreased population of neurons?
Ross, M. H., Galaburda, A. M., & Kemper, T. L. (1984) · Neurology · doi:10.1212/wnl.34.7.909 · Cited by 191
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
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
Hibaoui, Y., Grad, I., Letourneau, A., Sailani, M. R., Dahoun, S., Santoni, F. A., Gimelli, S., Guipponi, M., Pelte, M. F., Béna, F., et al. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201302848 · Cited by 170
Amano, K., Sago, H., Uchikawa, C., Suzuki, T., Kotliarova, S. E., Nukina, N., Epstein, C. J., & Yamakawa, K. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh154 · Cited by 146
Huo, H.-Q., Qu, Z.-Y., Yuan, F., Ma, L., Yao, L., Xu, M., Hu, Y., Ji, J., Bhattacharyya, A., Zhang, S.-C., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.02.001 · Cited by 122
Self-citationHyperkalemia during Anesthesia
Wisniewski, K. E., Laure‐Kamionowska, M., & Wisniewski, H. M. (1984) · New England Journal of Medicine · doi:10.1056/nejm198411013111818 · Cited by 105
Bowers, M., Liang, T., Gonzalez-Bohorquez, D., Zocher, S., Jaeger, B. N., Kovacs, W. J., Röhrl, C., Cramb, K. M. L., Winterer, J., Kruse, M., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.04.002 · Cited by 104
Broadgate, S., Thomson, R. E., Pellicano, F., Tartaglia, M. A., Pontikis, C. C., Cooper, J. D., & Iwata, T. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.11.035 · Cited by 94
Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons
Xiang, Y., Tanaka, Y., Patterson, B., Hwang, S., Hysolli, E., Çakır, B., Kim, K., Wang, W., Kang, Y., Clement, E. M., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.05.016 · Cited by 93
Alves-Sampaio, A., Troca-Marín, J. A., & Montesinos, M. L. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3457-10.2010 · Cited by 88
Biometry of Face and Brain in Fetuses with Trisomy 21
Guihard-Costa, A.-M., Khung‐Savatovsky, S., Delbecque, K., Ménez, F., & Delezoide, A. (2005) · Pediatric Research · doi:10.1203/01.pdr.0000190580.88391.9a · Cited by 85
Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly
Wang, L., Li, Z., Sievert, D., Smith, D. E. C., Mendes, M. I. S., Chen, D. Y., Stanley, V., Ghosh, S. G., Wang, Y., Kara, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17454-4 · Cited by 85
Self-citationBhattacharyya, A., McMillan, E., Chen, S. I., Wallace, K., & Svendsen, C. N. (2009) · Developmental Neuroscience · doi:10.1159/000236899 · Cited by 79
Self-citationSaito, Y., Oka, A., Mizuguchi, M., Motonaga, K., Mori, Y., Becker, L. E., Arima, K., Miyauchi, J., & Takashima, S. (2000) · Acta Neuropathologica · doi:10.1007/s004010000230 · Cited by 65
OLIG2 over-expression impairs proliferation of human Down syndrome neural progenitors
Lu, J., Lian, G., Zhou, H., Esposito, G., Steardo, L., Delli-Bovi, L. C., Hecht, J. L., Lu, Q. R., & Sheen, V. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds052 · Cited by 63
Serial quantitative CT analysis of brain morphometrics in adult Down's syndrome at different ages
Schapiro, M. B., Luxenberg, J. S., Kaye, J. A., Haxby, J. V., Friedland, R. P., & Рапопорт, С. И. (1989) · Neurology · doi:10.1212/wnl.39.10.1349 · Cited by 63
Zhang, X., Zhang, Y., Zhu, X., Purmann, C., Haney, M. S., Ward, T., Khechaduri, A., Yao, J., Weissman, S. M., & Urban, A. E. (2018) · Nature Communications · doi:10.1038/s41467-018-07766-x · Cited by 57
Self-citationPuoliväli, T., Palva, S., & Palva, J. M. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.108654 · Cited by 47
Johnstone, M., Vasistha, N. A., Barbu, M. C., Dando, O., Burr, K., Christopher, E., Glen, S., Robert, C., Fetit, R., MacLeod, K. G., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0292-1 · Cited by 43
Pan, X., Chang, X., Leung, C., Zhou, Z., Cao, F., Xie, W., & Jia, Z. (2015) · Molecular Brain · doi:10.1186/s13041-015-0124-z · Cited by 40
Yuan, F., Chen, X., Fang, K.-H., Wang, Y., Lin, M., Xu, S., Huo, H.-Q., Xu, M., Ma, L., Chen, Y., et al. (2018) · eLife · doi:10.7554/elife.37382 · Cited by 36
Self-citationZhang, L., Huang, Y., Chen, J.-Y., Ding, Y.-Q., & Song, N.-N. (2015) · Brain Research · doi:10.1016/j.brainres.2014.10.060 · Cited by 31
Human neural stem cells: a new tool for studying cortical development in Down's syndrome
Bhattacharyya, A., & Svendsen, C. N. (2003) · Genes Brain & Behavior · doi:10.1034/j.1601-183x.2003.00025.x · Cited by 27
Self-citationPérez-Núñez, R., Barraza, N., González‐Jamett, A. M., Cárdenas, A. M., Barnier, J., & Caviedes, P. A. (2016) · Neurotoxicity Research · doi:10.1007/s12640-016-9613-9 · Cited by 26
Guedj, F., Pennings, J. L. A., Wick, H. C., & Bianchi, D. W. (2014) · Brain Pathology · doi:10.1111/bpa.12151 · Cited by 23
Expression and significance of DSCAM in the cerebral cortex of APP transgenic mice
Jia, Y.-L., Jing, L., Li, J.-Y., Lu, J., Han, R. F., Wang, S., Peng, T., & Jia, Y. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.01.028 · Cited by 18
Self-citationFinak, G., McDavid, A., Yajima, M., et al. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/020842 · Cited by 13
Zhang, X., Zhang, Y., Zhu, X., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/182451 · Cited by 10
Self-citationWang, L., Li, Z., Sievert, D., Smith, D. E. C., Mendes, M. I., Chen, D. Y., Stanley, V., Ghosh, S., Wang, Y., Kara, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21448-1
Self-citationXu, R., Brawner, A. T., Li, S., Liu, J., Kim, H., Xue, H., Pang, Z. P., Kim, W.-Y., Hart, R. P., Liu, Y., et al. (2018) · doi:10.1101/462739
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Lu, K., Hong, Y., Tao, M., Shen, L., Zheng, Z., Fang, K.-H., Yuan, F., Xu, M., Wang, C., Zhu, D., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216364 · Cited by 59
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Metadata
- Authors
- Tang, X.-Y., Xu, L., Wang, J., Hong, Y., Wang, Y., Zhu, Q., Wang, D., Zhang, X.-Y., Liu, C.-Y., Fang, K.-H., Han, X., Wang, S., Wang, X., Xu, M., Bhattacharyya, A., Guo, X., Lin, M., & Liu, Y.
- Affiliations
- State Key Laboratory of Reproductive Medicine (CN)
- Nanjing Medical University (CN)
- Xiamen University (CN)
- University of Wisconsin–Madison (US)
- Corresponding author
- Guo, Xing
- Lin, Mingyan
- Liu, Yan
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2021-06-15
- Volume
- 131
- Issue
- 12
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC8203468
- OpenAlex
- W3158718113
- Cited by
- 143
- References
- 64
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 28 · 2023: 34 · 2022: 30 · 2021: 6
- FWCI
- 21.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Sciences (XDA16010306)
- Government of Jiangsu Province
- National Key Research and Development Program of China (2019YFA0802703)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- Down syndrome, Dscam, PAK1, neurogenesis, brain organoids, iPSC-derived organoids, cortical development, CRISPR interference, small molecule inhibitors, cognitive impairment, in vitro disease model
- MeSH terms
- Cell Line, Cerebral Cortex, Down Syndrome, Humans, Organoids, Signal Transduction, Cell Adhesion Molecules, p21-Activated Kinases, Neurogenesis, Induced Pluripotent Stem Cells
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