Single cell sequencing reveals low levels of aneuploidy across mammalian tissues
Open accessAbstract
Significance: Aneuploidy refers to the gain or loss of individual chromosomes within a cell. Typically, aneuploidy is associated with detrimental consequences at both the cellular and organismal levels. However, reports of high levels of aneuploidy in the brain and liver suggested that aneuploidy might play a positive role in these organs. Here we use single cell sequencing to determine the prevalence of aneuploidy in somatic tissues. We find that aneuploidy is a rare occurrence in the liver and brain and is no more prevalent in these tissues than in skin. Our results demonstrate high karyotypic stability in somatic tissues, arguing against a role for aneuploidy in organ function and reinforcing its adverse effects at the cellular and organismal levels.
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Early successes include parallel measurement of the transcriptome and either the genome (DR-seq and G&T-seq), the methylome (scM&T-seq, an adaptation of G&T-seq), or the proteome.
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Emerging experimental frameworks now allow simultaneous measurement of multiple omic data types from the same single cell.
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From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [211]
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Cites
Protein aggregation and neurodegenerative disease
Ross, C. A., & Poirier, M. A. (2004) · Nature Medicine · doi:10.1038/nm1066 · Cited by 3,454 · see citing works
The spindle-assembly checkpoint in space and time
Musacchio, A., & Salmon, E. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2163 · Cited by 2,227 · see citing works
A mechanism linking extra centrosomes to chromosomal instability
Ganem, N. J., Godinho, S. A., & Pellman, D. S. (2009) · Nature · doi:10.1038/nature08136 · Cited by 1,427 · see citing works
Effects of Aneuploidy on Cellular Physiology and Cell Division in Haploid Yeast
Torres, E. M., Sokolsky, T., Tucker, C. M., Chan, L. Y., Boselli, M., Dunham, M. J., & Amon, A. (2007) · Science · doi:10.1126/science.1142210 · Cited by 935 · see citing works
Self-citationDavoli, T., Xu, A. W., Mengwasser, K. E., Sack, L. M., Yoon, J. C., Park, P. J., & Elledge, S. J. (2013) · Cell · doi:10.1016/j.cell.2013.10.011 · Cited by 815 · see citing works
Aneuploidy and Isochromosome Formation in Drug-Resistant <i>Candida albicans</i>
Selmecki, A., Forche, A., & Berman, J. (2006) · Science · doi:10.1126/science.1128242 · Cited by 733 · see citing works
BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice
Baker, D. J., Jeganathan, K. B., Cameron, J. D., Thompson, M., Juneja, S., Kopecka, A., Kumar, R., Jenkins, R. B., de Groen, P. C., Roche, P., et al. (2004) · Nature Genetics · doi:10.1038/ng1382 · Cited by 731 · see citing works
Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells
Williams, B. R., Prabhu, V. R., Hunter, K. E., Glazier, C. M., Whittaker, C. A., Housman, D. E., & Amon, A. (2008) · Science · doi:10.1126/science.1160058 · Cited by 665 · see citing works
Self-citationHassold, T. J., & Jacobs, P. A. (1984) · Annual Review of Genetics · doi:10.1146/annurev.ge.18.120184.000441 · Cited by 653 · see citing works
Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B
Hanks, S., Coleman, K., Reid, S., Plaja, A., Firth, H., Fitzpatrick, D., Kidd, A., Méhes, K., Nash, R., Robin, N. H., et al. (2004) · Nature Genetics · doi:10.1038/ng1449 · Cited by 627 · see citing works
Mosaic Copy Number Variation in Human Neurons
McConnell, M. J., Lindberg, M. R., Brennand, K. J., Piper, J. C., Voet, T., Cowing-Zitron, C., Shumilina, S., Lasken, R. S., Vermeesch, J. R., Hall, I. M., et al. (2013) · Science · doi:10.1126/science.1243472 · Cited by 551 · see citing works
The ploidy conveyor of mature hepatocytes as a source of genetic variation
Duncan, A. W., Taylor, M. H., Hickey, R. D., Hanlon Newell, A. E., Lenzi, M. L., Olson, S. B., Finegold, M. J., & Grompe, M. (2010) · Nature · doi:10.1038/nature09414 · Cited by 525 · see citing works
The Causes and Consequences of Polyploidy in Normal Development and Cancer
Davoli, T., & de Lange, T. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154234 · Cited by 432 · see citing works
Chromosomal duplication is a transient evolutionary solution to stress
Yona, A. H., Manor, Y. S., Herbst, R. H., Romano, G. H., Mitchell, A., Kupiec, M., Pilpel, Y., & Dahan, O. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211150109 · Cited by 376 · see citing works
Identification of Aneuploidy-Selective Antiproliferation Compounds
Tang, Y., Williams, B. R., Siegel, J. J., & Amon, A. (2011) · Cell · doi:10.1016/j.cell.2011.01.017 · Cited by 347 · see citing works
Self-citationChromosomal variation in neurons of the developing and adult mammalian nervous system
Rehen, S. K., McConnell, M. J., Kaushal, D., Kingsbury, M. A., Yang, A. H., & Chun, J. J. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231487398 · Cited by 328 · see citing works
Constitutional Aneuploidy in the Normal Human Brain
Rehen, S. K., Yung, Y. C., McCreight, M. P., Kaushal, D., Yang, A. H., Almeida, B. S. V., Kingsbury, M. A., Cabral, K. M. D. S., McConnell, M. J., Anliker, B., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4560-04.2005 · Cited by 320 · see citing works
Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes
Guidotti, J.-E., Brégerie, O., Robert, A., Debey, P., Brechot, C., & Desdouets, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300982200 · Cited by 315 · see citing works
Aneuploidy causes proteotoxic stress in yeastPreprint
Oromendia, A. B., Dodgson, S. E., & Amon, A. (2012) · Genes & Development · doi:10.1101/gad.207407.112 · Cited by 307 · see citing works
Self-citationGeneration of neuronal variability and complexity
Muotri, A. R., & Gage, F. H. (2006) · Nature · doi:10.1038/nature04959 · Cited by 271 · see citing works
Ha, G., Roth, A. J. L., Lai, D., Bashashati, A., Ding, J., Goya, R., Giuliany, R., Rosner, J., Oloumi, A., Shumansky, K., et al. (2012) · Genome Research · doi:10.1101/gr.137570.112 · Cited by 269 · see citing works
Merotelic kinetochore attachment: causes and effects
Gregáň, J., Poláková, S., Zhang, L., Tolić, I. M., & Cimini, D. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.01.003 · Cited by 251 · see citing works
Kahlem, P., Sultan, M., Herwig, R., Steinfath, M., Balzereit, D., Eppens, B., Saran, N. G., Pletcher, M. T., South, S. T., Stetten, G., et al. (2004) · Genome Research · doi:10.1101/gr.1951304 · Cited by 249 · see citing works
Aneuploidy and Confined Chromosomal Mosaicism in the Developing Human Brain
Yurov, Y. B., Iourov, I. Y., Vorsanova, S. G., Liehr, T., Kolotii, A. D., Kutsev, S. I., Pellestor, F., Beresheva, A. K., Ia, D., Сергеевич, К. В., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000558 · Cited by 226 · see citing works
Somatic mutations in aging, cancer and neurodegeneration
Kennedy, S. R., Loeb, L. A., & Herr, A. J. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.10.009 · Cited by 216 · see citing works
Iourov, I. Y., Vorsanova, S. G., Liehr, T., & Yurov, Y. B. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.01.003 · Cited by 209 · see citing works
Frequent Aneuploidy Among Normal Human Hepatocytes
Duncan, A. W., Hanlon Newell, A. E., Smith, L., Wilson, E. M., Olson, S. B., Thayer, M. J., Strom, S. C., & Grompe, M. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.10.029 · Cited by 197 · see citing works
Selective Cell Death of Hyperploid Neurons in Alzheimer’s Disease
Arendt, T., Brückner, M. K., Mosch, B., & Lösche, A. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090955 · Cited by 187 · see citing works
Aneuploidy as a mechanism for stress-induced liver adaptation
Duncan, A. W., Newell, A. E. H., Bi, W., Finegold, M. J., Olson, S. B., Beaudet, A. L., & Grompe, M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64026 · Cited by 185 · see citing works
Aneuploid neurons are functionally active and integrated into brain circuitry
Kingsbury, M. A., Friedman, B., McConnell, M. J., Rehen, S. K., Yang, A. H., Kaushal, D., & Chun, J. J. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408171102 · Cited by 175 · see citing works
Liver tetraploidization is controlled by a new process of incomplete cytokinesis
Margall-Ducos, G., Celton-Morizur, S., Couton, D., Brégerie, O., & Desdouets, C. (2007) · Journal of Cell Science · doi:10.1242/jcs.016907 · Cited by 170 · see citing works
Chromosome Segregation Defects Contribute to Aneuploidy in Normal Neural Progenitor Cells
Yang, A. H., Kaushal, D., Rehen, S. K., Kriedt, K., Kingsbury, M. A., McConnell, M. J., & Chun, J. J. M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-32-10454.2003 · Cited by 130 · see citing works
Chromosome-specific accumulation of aneuploidy in the aging mouse brain
Faggioli, F., Wang, T., Vijg, J., & Montagna, C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds375 · Cited by 106 · see citing works
Individual variability in the stress response of C57BL/6J male mice correlates with trait anxiety
Jakovcevski, M., Schachner, M., & Morellini, F. (2007) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00345.x · Cited by 74 · see citing works
Zou, Y., Bao, Q., Kumar, S., Hu, M., Wang, G., & Dai, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030675 · Cited by 64 · see citing works
Pack, S., Weil, R. J., Vortmeyer, A. O., et al. (2005) · Cell Cycle · doi:10.4161/cc.4.12.2153 · Cited by 48 · see citing works
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- Authors
- Knouse, K. A., Wu, J., Whittaker, C. A., & Amon, A.
- Affiliations
- Harvard University (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-09-02
- Volume
- 111
- Issue
- 37
- Pages
- 13409-13414
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4169915
- OpenAlex
- W2066803056
- Cited by
- 314
- References
- 36
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 30 · 2023: 20 · 2022: 24 · 2021: 37 · 2020: 25 · 2019: 33 · 2018: 32 · 2017: 30 · 2016: 34 · 2015: 20 · 2014: 1
- FWCI
- 18.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (P50AG005134)
- National Cancer Institute (U54CA143874, P30CA014051)
- National Institute of General Medical Sciences (T32GM007753, T32GM007287)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- aneuploidy, whole-chromosome aneuploidy, single-cell genomics, liver, brain, skin, karyotype, cancer, mouse tissues, human tissue, natural selection
- MeSH terms
- Aneuploidy, Animals, Brain, Humans, Liver, Male, Mammals, Organ Specificity, Skin, Reproducibility of Results, Sequence Analysis, DNA, Mice, Single-Cell Analysis
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