Cell Type-Specific Transcriptomics Reveals that Mutant Huntingtin Leads to Mitochondrial RNA Release and Neuronal Innate Immune Activation
Open accessAbstract
The mechanisms by which mutant huntingtin (mHTT) leads to neuronal cell death in Huntington's disease (HD) are not fully understood. To gain new molecular insights, we used single nuclear RNA sequencing (snRNA-seq) and translating ribosome affinity purification (TRAP) to conduct transcriptomic analyses of caudate/putamen (striatal) cell type-specific gene expression changes in human HD and mouse models of HD. In striatal spiny projection neurons, the most vulnerable cell type in HD, we observe a release of mitochondrial RNA (mtRNA) (a potent mitochondrial-derived innate immunogen) and a concomitant upregulation of innate immune signaling in spiny projection neurons. Further, we observe that the released mtRNAs can directly bind to the innate immune sensor protein kinase R (PKR). We highlight the importance of studying cell type-specific gene expression dysregulation in HD pathogenesis and reveal that the activation of innate immune signaling in the most vulnerable HD neurons provides a novel framework to understand the basis of mHTT toxicity and raises new therapeutic opportunities.
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?
HTT gene mutations trigger a cascade of molecular events, including transcriptional dysregulation, impaired protein homoeostasis, and disrupted intracellular transport.
“HTT gene mutations trigger a cascade of molecular events, including transcriptional dysregulation, impaired protein homoeostasis, and disrupted intracellular transport.200”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [200]
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
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 · see citing works
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
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
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
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · see citing works
Enrichr: a comprehensive gene set enrichment analysis web server 2016 update
Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S. L., Jagodnik, K. M., Lachmann, A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw377 · Cited by 10,799 · see citing works
Fast, sensitive and accurate integration of single-cell data with Harmony
Korsunsky, I., Millard, N., Fan, J., Slowikowski, K., Zhang, F., Wei, K., Baglaenko, Y., Brenner, M., Loh, P.-R., & Raychaudhuri, S. (2019) · Nature Methods · doi:10.1038/s41592-019-0619-0 · Cited by 10,488 · see citing works
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366 · see citing works
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma’ayan, A. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-128 · Cited by 7,814 · see citing works
A General Framework for Weighted Gene Co-Expression Network Analysis
Zhang, B., & Horvath, S. (2005) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1128 · Cited by 5,684 · see citing works
Dimensionality reduction for visualizing single-cell data using UMAP
Becht, E., McInnes, L., Healy, J., Dutertre, C.-A., Kwok, I. W. H., Ng, L. G., Ginhoux, F., & Newell, E. W. (2019) · Nature Biotechnology · doi:10.1038/nbt.4314 · Cited by 5,358 · see citing works
Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81369-0 · Cited by 3,073 · see citing works
Shah, M. A., Datson, N. A., Srinidhi, L., Stanton, V. P., MacDonald, M. E., Allard, M. W., Youngman, S., Am, F., Mott, R., Draths, K., et al. (1993) · Cell · Cited by 3,055 · see citing works
Molecular Architecture of the Mouse Nervous System
Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L. E., La Manno, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.021 · Cited by 2,995 · see citing works
Neuropathological Classification of Huntingtonʼs Disease
Vonsattel, J., Myers, R. H., STEVENS, T. J., Ferrante, R. J., Bird, E. D., & Richardson, E. P. (1985) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198511000-00003 · Cited by 2,598 · see citing works
Single-cell transcriptomic analysis of Alzheimer’s disease
Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1195-2 · Cited by 2,568 · see citing works
Self-citationBatch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors
Haghverdi, L., Lun, A. T. L., Morgan, M. D., & Marioni, J. C. (2018) · Nature Biotechnology · doi:10.1038/nbt.4091 · Cited by 2,416 · see citing works
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975 · see citing works
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 1,847 · cited 4× · see citing works
“Our profiling studies (Figures 1, 2, 3, 4, and 5) indicate that, although dSPNs, iSPNs, Foxp2/Olfm3 neurons, and astroglia of both the R6/2 and zQ175DN mouse HD models recapitulate many of the gene expression changes occurring in these cells of grade 2–4 human HD tissue, this is less so for other cell types, such as mi…”
BackgroundInfluentialRapid single-step induction of functional neurons from human pluripotent stem cells
Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Marro, S., Patzke, C., Acuna, C., Covy, J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.029 · Cited by 1,644 · see citing works
Neuronal subtype specification in the cerebral cortex
Molyneaux, B. J., Arlotta, P., Menezes, J. R. L., & Macklis, J. D. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2151 · Cited by 1,632 · see citing works
Saudou, F., Finkbeiner, S. M., Devys, D., & Greenberg, M. E. (1998) · Cell · doi:10.1016/s0092-8674(00)81782-1 · Cited by 1,598 · see citing works
ChEA3: transcription factor enrichment analysis by orthogonal omics integration
Keenan, A. B., Torre, D., Lachmann, A., Leong, A. K., Wojciechowicz, M. L., Utti, V., Jagodnik, K. M., Kropiwnicki, E., Wang, Z., & Ma’ayan, A. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz446 · Cited by 1,136 · see citing works
A translational profiling approach for the molecular characterization of CNS cell types
Heiman, M., Schaefer, A., Gong, S., Peterson, J. D., Day, M., Ramsey, K. E., Suárez-Fariñas, M., Schwarz, C., Stephan, D. A., Surmeier, D. J., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.028 · Cited by 1,134 · see citing works
Self-citationThe neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia
Gerfen, C. R. (1992) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.15.030192.001441 · Cited by 1,004 · see citing works
Differential loss of striatal projection neurons in Huntington disease.
Reiner, A. J., Albin, R. L., Anderson, K. D., D’Amato, C. J., Penney, J. B., & Young, A. B. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.15.5733 · Cited by 999 · see citing works
ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments
Lachmann, A., Xu, H., Krishnan, J., Berger, S., Mazloom, A. R., & Ma’ayan, A. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq466 · Cited by 997 · see citing works
Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production
White, M. J., McArthur, K., Metcalf, D., Lane, R. M., Cambier, J. C., Herold, M. J., van Delft, M. F., Bedoui, S., Lessene, G., Ritchie, M. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.036 · Cited by 983 · see citing works
Alvarez, M. J., Shen, Y., Giorgi, F. M., Lachmann, A., Ding, B. B., Ye, B. H., & Califano, A. (2016) · Nature Genetics · doi:10.1038/ng.3593 · Cited by 966 · see citing works
Recruitment of human muscleblind proteins to (CUG)n expansions associated with myotonic dystrophy
Miller, J. W., Urbinati, C. R., Teng‐umnuay, P., Stenberg, M. G., Byrne, B. J., Thornton, C. A., & Swanson, M. S. (2000) · The EMBO Journal · doi:10.1093/emboj/19.17.4439 · Cited by 937 · see citing works
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925 · see citing works
Application of a translational profiling approach for the comparative analysis of CNS cell types
Doyle, J. P., Dougherty, J. D., Heiman, M., Schmidt, E. F., Stevens, T. R., Ma, G., Bupp, S., Shrestha, P., Shah, R. D., Doughty, M. L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.029 · Cited by 912 · see citing works
Self-citationEfficient integration of heterogeneous single-cell transcriptomes using Scanorama
Hie, B., Bryson, B. D., & Berger, B. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0113-3 · Cited by 853 · see citing works
Molecular Mechanisms and Potential Therapeutical Targets in Huntington's Disease
Zuccato, C., Valenza, M., & Cattaneo, E. (2010) · Physiological Reviews · doi:10.1152/physrev.00041.2009 · Cited by 848 · see citing works
Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
Rongvaux, A., Jackson, R., Harman, C. C. D., Li, T., West, A. P., de Zoete, M. R., Wu, Y., Yordy, B., Lakhani, S. A., Kuan, C.-Y., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.037 · Cited by 847 · see citing works
Regional and cellular gene expression changes in human Huntington's disease brain
Hodges, A., Strand, A. D., Aragaki, A. K., Kuhn, A., Sengstag, T., Hughes, G., Elliston, L. A., Hartog, C., Goldstein, D. R., Thu, D., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl013 · Cited by 804 · see citing works
Graybiel, A. M., & Ragsdale, C. W. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.11.5723 · Cited by 784 · see citing works
Decreased expression of striatal signaling genes in a mouse model of Huntington's disease
Luthi‐Carter, R. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.9.1259 · Cited by 723 · see citing works
Mitochondrial double-stranded RNA triggers antiviral signalling in humans
Dhir, A., Dhir, S., Borowski, L. S., Jimenez, L., Teitell, M., Rötig, A., Crow, Y. J., Rice, G. I., Duffy, D., Tamby, C., et al. (2018) · Nature · doi:10.1038/s41586-018-0363-0 · Cited by 631 · see citing works
Targeting cells with single vectors using multiple-feature Boolean logic
Fenno, L. E., Mattis, J., Ramakrishnan, C., Hyun, M., Lee, S. Y., He, M., Tucciarone, J., Selimbeyoglu, A., Berndt, A., Grosenick, L., et al. (2014) · Nature Methods · doi:10.1038/nmeth.2996 · Cited by 557 · see citing works
Human ADAR1 Prevents Endogenous RNA from Triggering Translational Shutdown
Chung, H., Calis, J. J. A., Wu, X., Sun, T., Yu, Y., Sarbanes, S. L., Dao Thi, V. L., Shilvock, A. R., Hoffmann, H.-H., Rosenberg, B. R., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.038 · Cited by 538 · see citing works
CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset
Lee, J., Correia, K., Loupe, J. M., Kim, K., Barker, D., Hong, E. P., Chao, M. J., Long, J. D., Lucente, D. E., Vonsattel, J. P., et al. (2019) · Cell · doi:10.1016/j.cell.2019.06.036 · Cited by 532 · see citing works
Menalled, L., Sison, J. D., Dragatsis, I., Zeitlin, S. O., & Chesselet, M. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10776 · Cited by 528 · see citing works
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
Musiek, E. S., Lim, M. M., Yang, G., Bauer, A. Q., Qi, L., Lee, Y., Roh, J. H., Ortiz-Gonzalez, X., Dearborn, J. T., Culver, J. P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70317 · Cited by 524 · see citing works
Cell type–specific mRNA purification by translating ribosome affinity purification (TRAP)
Heiman, M., Kulicke, R., Fenster, R. J., Greengard, P., & Heintz, N. (2014) · Nature Protocols · doi:10.1038/nprot.2014.085 · Cited by 498 · see citing works
Self-citationMenalled, L., Kudwa, A. E., Miller, S., Fitzpatrick, J., Watson-Johnson, J., Keating, N., Ruiz, M. C., Mushlin, R. A., Alosio, W., McConnell, K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049838 · Cited by 470 · see citing works
The harmonic mean <i>p</i> -value for combining dependent tests
Wilson, D. J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814092116 · Cited by 449 · see citing works
MANLEY, K. M., Shirley, T. L., Flaherty, L. A., & Messer, A. C. (1999) · Nature Genetics · doi:10.1038/70598 · Cited by 415 · see citing works
Tissue-resident memory T cells populate the human brain
Smolders, J., Heutinck, K. M., Fransen, N. L., Remmerswaal, E. B. M., Hombrink, P., ten Berge, I. J. M., van Lier, R. A. W., Huitinga, I., & Hamann, J. (2018) · Nature Communications · doi:10.1038/s41467-018-07053-9 · Cited by 406 · see citing works
Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse
Wheeler, V. C. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.1.115 · Cited by 395 · see citing works
Efficient Test and Visualization of Multi-Set Intersections
Wang, M., Zhao, Y., & Zhang, B. (2015) · Scientific Reports · doi:10.1038/srep16923 · Cited by 395 · see citing works
Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice
Langfelder, P., Cantle, J. P., Chatzopoulou, D., Wang, N., Gao, F., Al-Ramahi, I., Lu, X.-H., Ramos, E. M., El-Zein, K., Zhao, Y., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4256 · Cited by 385 · see citing works
Self-citationAlbin, R. L., Reiner, A. J., Anderson, K. D., Dure, L. S., Handelin, B., Balfour, R., Whetsell, W. O., Penney, J. B., & Young, A. B. (1992) · Annals of Neurology · doi:10.1002/ana.410310412 · Cited by 368 · see citing works
Birch‐Machin, M. A., & Turnbull, D. M. (2001) · Methods in cell biology · doi:10.1016/s0091-679x(01)65006-4 · Cited by 367 · see citing works
Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms
Bradford, J. W., Shin, J., Redd, M. A., Wang, C.-E., Li, X.-J., & Li, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911503106 · Cited by 362 · see citing works
RAN Translation in Huntington Disease
Báñez-Coronel, M., Ayhan, F., Tarabochia, A. D., Zu, T., Pérez, B., Tusi, S. K., Pletniková, O., Borchelt, D., Ross, C. A., Margolis, R. L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.038 · Cited by 356 · see citing works
Early Loss of Neostriatal Striosome Neurons in Huntingtonʼs Disease
Hedreen, J. C., & Folstein, S. E. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199501000-00013 · Cited by 327 · see citing works
When is hub gene selection better than standard meta-analysis?
Langfelder, P., Mischel, P. S., & Horvath, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061505 · Cited by 313 · see citing works
The corticostriatal pathway in Huntington's disease
Cepeda, C., Wu, N.-P., André, V. M., Cummings, D. M., & LEVINE, M. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.11.001 · Cited by 309 · see citing works
Heikkinen, T., Lehtimäki, K. K., Vartiainen, N. E., Puoliväli, J. T., Hendricks, S. J., Glaser, J. R., Bradaïa, A., Wadel, K., Touller, C., Kontkanen, O., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050717 · Cited by 273 · see citing works
Chen, J. Y., Penco, S., Ostrowski, J., Balaguer, P., Pons, M., Starrett, J. E. J., Reczek, P. R., Chambon, P., & Gronemeyer, H. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07102.x · Cited by 256 · see citing works
Dragileva, E., Hendricks, A. E., Teed, A. M., Gillis, T., Lopez, E., Friedberg, E. C., Kucherlapati, R., Edelmann, W., Lunetta, K. L., MacDonald, M. E., et al. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.09.014 · Cited by 247 · see citing works
PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs
Kim, Y., Park, J., Kim, S., Kim, M. A., Kang, M., Kwak, C. S., Kang, M., Kim, B., Rhee, H., & Kim, V. N. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.029 · Cited by 242 · see citing works
MEURS, E. F., Watanabe, Y., Kadereit, S., et al. (1992) · Journal of Virology · doi:10.1128/jvi.66.10.5805-5814.1992 · Cited by 241 · see citing works
Unravelling and Exploiting Astrocyte Dysfunction in Huntington’s Disease
Khakh, B. S., Beaumont, V., Cachope, R., Muñoz-Sanjuán, I., Goldman, S. A., & Grantyn, R. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.05.002 · Cited by 233 · see citing works
DNA instability in postmitotic neurons
Gonitel, R., Moffitt, H., Sathasivam, K., Woodman, B., Detloff, P., Faull, R., & Bates, G. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0800048105 · Cited by 225 · see citing works
Menalled, L., Sison, J. D., Wu, Y. N., Olivieri, M., Li, X., Li, H., Zeitlin, S. O., & Chesselet, M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-18-08266.2002 · Cited by 221 · see citing works
Cheng, W., Wang, S., Mestre, A. A., Fu, C., Makarem, A. O., Xian, F., Hayes, L. R., Lopez-Gonzalez, R., Drenner, K., Jiang, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02495-z · Cited by 203 · see citing works
Brimblecombe, K. R., & Cragg, S. J. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00333 · Cited by 201 · see citing works
Cicchetti, F., Prensa, L., Wu, Y., & Parent, A. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00039-4 · Cited by 192 · see citing works
Tom70 mediates activation of interferon regulatory factor 3 on mitochondria
Liu, X.-Y., Wei, B., Shi, H.-X., Shan, Y.-F., & Wang, C. (2010) · Cell Research · doi:10.1038/cr.2010.103 · Cited by 171 · see citing works
Presto scales Wilcoxon and auROC analyses to millions of observationsPreprint
Korsunsky, I., Nathan, A., Millard, N., & Raychaudhuri, S. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/653253 · Cited by 159 · see citing works
Sawiak, S. J., Wood, N. I., Williams, G. B., Morton, A. J., & Carpenter, T. A. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.09.016 · Cited by 150 · see citing works
Alfadhel, M., Almuntashri, M., Jadah, R. H. S., Bashiri, F. A., Rifai, M. A., Shalaan, H. A., Balwi, M. A. A., Rumayan, A. A., Eyaid, W., & Altwaijri, W. A. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-83 · Cited by 150 · see citing works
3‐Nitropropionic Acid Toxicity in the Striatum
Wüllner, U., Young, A. B., Penney, J. B., et al. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63051772.x · Cited by 137 · see citing works
A Spatiomolecular Map of the Striatum
Märtin, A., Calvigioni, D., Tzortzi, O., Fuzik, J., Wärnberg, E., & Meletis, K. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.096 · Cited by 127 · see citing works
Benn, C., Landles, C., He, L., Strand, A. D., Woodman, B., Sathasivam, K., Li, S.-H., Ghazi‐Noori, S., Hockly, E., Faruque, S. M. N. N., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi340 · Cited by 123 · see citing works
Bolam, J. P., Izzo, P. N., & Graybiel, A. M. (1988) · Neuroscience · doi:10.1016/0306-4522(88)90073-5 · Cited by 117 · see citing works
CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs
Schatton, D., Pla‐Martín, D., Marx, M., Hansen, H., Mourier, A., Nemazanyy, I., Pessia, A., Zentis, P., Corona, T., Kondylis, V., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201607019 · Cited by 96 · see citing works
Wertz, M. H., Mitchem, M. R., Pineda, S. S., Hachigian, L. J., Lee, H., Lau, V., Powers, A. E., Kulicke, R., Madan, G. K., Colic, M., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.004 · Cited by 94 · see citing works
Self-citationRational design of RAR‐selective ligands revealed by RARβ crystal stucture
Germain, P., Kammerer, S., Pérez‐Santín, E., Peluso‐Iltis, C., Tortolani, D. R., Zusi, F. C., Starrett, J. E. J., Lapointe, P., Daris, J., Marinier, A., et al. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400235 · Cited by 91 · see citing works
Coexpression of junctophilin type 3 and type 4 in brain
Nishi, M., Sakagami, H., Komazaki, S., et al. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(03)00341-3 · Cited by 84 · see citing works
The oxindole/imidazole derivative C16 reduces in vivo brain PKR activation
Ingrand, S., Barrier, L., Lafay-Chebassier, C., Fauconneau, B., Page, G., & Hugon, J. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.08.022 · Cited by 80 · see citing works
Dedoni, S., Olianas, M. C., & Onali, P. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07046.x · Cited by 76 · see citing works
Thiamine deficiency in infants: MR findings in the brain.
Kornreich, L., Bron-Harlev, E., Hoffmann, C., Schwarz, M., Konen, O., Schoenfeld, T., Straussberg, R., Nahum, E., Abu‐Kishk, I., Eshel, G. M., et al. (2005) · PubMed Central · Cited by 54 · see citing works
A geometric approach to characterize the functional identity of single cells
Mohammadi, S., Ravindra, V., Gleich, D. F., & Grama, A. Y. (2018) · Nature Communications · doi:10.1038/s41467-018-03933-2 · Cited by 51 · see citing works
Self-citationFranich, N. R., Hickey, M. A., Zhu, C., Osborne, G. F., Ali, N. S., Chu, T., Bove, N., Lemesre, V., Lerner, R. P., Zeitlin, S. O., et al. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24493 · Cited by 49 · see citing works
Niewiadomska-Cimicka, A., Krzyżosiak, A., Ye, T., Podlesny‐Drabiniok, A., Dembélé, D., Dollé, P., & Krężel, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0010-4 · Cited by 47 · see citing works
Wang, X., Fan, Z., Wang, B., Luo, J., & Ke, Z. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04978.x · Cited by 45 · see citing works
Schlehe, J. S., Journel, M. S. M., Taylor, K. P., Amodeo, K. D., & LaVoie, M. J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.05.007 · Cited by 33 · see citing works
Self-citationHachigian, L. J., Carmona, V., Fenster, R. J., Kulicke, R., Heilbut, A. M., Sittler, A., de Almeida, L. P., Mesirov, J. P., Gao, F., Kolaczyk, E. D., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.018 · Cited by 27 · see citing works
Self-citationConvergence of independent DISC1 mutations on impaired neurite growth via decreased UNC5D expression
Srikanth, P., Lagomarsino, V. N., Pearse, R. V., Liao, M., Ghosh, S. D., Nehme, R., Seyfried, N. T., Eggan, K. C., & Young‐Pearse, T. L. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0281-9 · Cited by 25 · see citing works
Crabtree, H. G. (1935) · Biochemical Journal · doi:10.1042/bj0292334 · Cited by 18 · see citing works
A multiresolution framework to characterize single-cell state landscapesPreprint
Mohammadi, S., Dávila-Velderrain, J., & Kellis, M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/746339 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Mohammadi S, Davila-Velderrain J, and Kellis M (2019). Multi-resolution single-cell state characterization via joint archetypal/network analysis. bioRxiv.
- Seabold JS, and Perktold J (2010). Statsmodels: Econometric and Statistical Modeling with Python. Paper presented at: Python in Science Conference (Austin, Texas).
Cited by
Sorted by citations
Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Endo, F., Kasai, A., Soto, J. S., Yu, X., Qu, Z., Hashimoto, H., Gradinaru, V., Kawaguchi, R., & Khakh, B. S. (2022) · Science · doi:10.1126/science.adc9020 · Cited by 560 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
Welch, G. M., Boix, C. A., Schmauch, E., Davila-Velderrain, J., Victor, M. B., Dileep, V., Bozzelli, P. L., Su, Q., Cheng, J. D., Lee, A., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo4662 · Cited by 84 · see citing works
Self-citationDeletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways
Ibanez, K. R., McFarland, K. N., Phillips, J., Allen, M., Lessard, C. B., Zobel, L., De La Cruz, E. G., Shah, S., Vo, Q., Wang, X., et al. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01044-1 · Cited by 18 · see citing works
- Authors
- Lee, H., Fenster, R. J., Pineda, S. S., Gibbs, W. S., Mohammadi, S., Davila-Velderrain, J., Garcia, F. J., Therrien, M., Novis, H. S., Gao, F., Wilkinson, H., Vogt, T., Kellis, M., LaVoie, M. J., & Heiman, M.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- California Institute of Technology (US)
- CHDI Foundation (US)
- Corresponding author
- Heiman, Myriam
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 107
- Issue
- 5
- Pages
- 891-908.e8
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC7486278
- OpenAlex
- W3042822579
- Cited by
- 279
- References
- 96
- Citations by year
- 2026: 40 · 2025: 45 · 2024: 60 · 2023: 47 · 2022: 49 · 2021: 31 · 2020: 6 · 2012: 1
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- JPB Foundation
- National Institutes of Health
- CHDI Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Huntington's disease, mutant huntingtin, PKR, medium spiny neurons, striatum, neuronal cell death, cell type-specific gene expression, innate immune signaling, neuroinflammation
- MeSH terms
- Huntingtin Protein, RNA, Mitochondrial, Animals, Humans, Huntington Disease, Immunity, Innate, Mutation, Neurons, Mice, Transcriptome
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
