Single-Cell Transcriptomics Characterizes Cell Types in the Subventricular Zone and Uncovers Molecular Defects Impairing Adult Neurogenesis
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Abstract
Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs regulate stem cell self-renewal and differentiation. We used comprehensive and untargeted single-cell RNA profiling to generate a molecular cell atlas of the largest germinal region of the adult mouse brain, the subventricular zone (SVZ). We characterized >20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we applied our single-cell approach to document decreased numbers of NSCs, reduced proliferation activity of progenitors, and perturbations in Wnt and BMP signaling pathways in mice lacking LRP2, an endocytic receptor required for SVZ maintenance. Our data provide a valuable resource to study adult neurogenesis and a proof of principle for the power of single-cell RNA sequencing to elucidate neural cell-type-specific alterations in loss-of-function models.
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Recently published transcriptomic studies showed aging-related downregulation of ribosomal genes in ASC and NSC, and upregulation in MG of aged and diseased brains.
“recently published transcriptomic studies showed an agingrelated downregulation of ribosomal genes in both ASC 14 and NSC 61 , and an upregulation in MG of both aged 62,63 and diseased brains 62,64 .”
From Single-cell transcriptomic profiling of the aging mouse brain (2019) · cites this paper as [63]
Cites
Fitting Linear Mixed-Effects Models Using <b>lme4</b>
Bates, D., Mächler, M., Bolker, B., & Walker, S. (2015) · Journal of Statistical Software · doi:10.18637/jss.v067.i01 · Cited by 86,835 · 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
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
SCANPY: large-scale single-cell gene expression data analysis
Wolf, F. A., Angerer, P., & Theis, F. J. (2018) · Genome Biology · doi:10.1186/s13059-017-1382-0 · Cited by 8,881 · see citing works
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110 · see citing works
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055 · see citing works
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
Reynolds, B. A., & Weiss, S. (1992) · Science · doi:10.1126/science.1553558 · Cited by 5,413 · see citing works
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · see citing works
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
La Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M. E., Lönnerberg, P., Furlan, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0414-6 · Cited by 4,118 · see citing works
Subventricular zone astrocytes are neural stem cells in the adult mammalian brain
Doetsch, F., Caillé, I., Lim, D. A., García-Verdugo, J. M., & Alvarez-Buylla, A. (1999) · Cell · doi:10.1016/s0092-8674(00)80783-7 · Cited by 3,898 · see citing works
Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions
Ming, G.-L., & Song, H. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.001 · Cited by 2,651 · see citing works
Doetsch, F. K., García‐Verdugo, J. M., & Álvarez-Buylla, A. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-13-05046.1997 · Cited by 1,909 · see citing works
Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells
Shen, Q., Goderie, S. K., Jin, L., Karanth, N., Sun, Y., Abramova, N. E., Vincent, P. A., Pumiglia, K. M., & Temple, S. (2004) · Science · doi:10.1126/science.1095505 · Cited by 1,538 · see citing works
Diffusion pseudotime robustly reconstructs lineage branching
Haghverdi, L., Büttner, M., Wolf, F. A., Buettner, F., & Theis, F. J. (2016) · Nature Methods · doi:10.1038/nmeth.3971 · Cited by 1,385 · see citing works
Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system
Marques, S., Zeisel, A., Codeluppi, S., van Bruggen, D., Mendanha Falcão, A., Xiao, L., Li, H., Häring, M., Hochgerner, H., Romanov, R. A., et al. (2016) · Science · doi:10.1126/science.aaf6463 · Cited by 1,246 · see citing works
Shen, Q., Wang, Y., Kokovay, E., Lin, G., Chuang, S.-M., Goderie, S. K., Roysam, B., & Temple, S. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.026 · Cited by 1,027 · see citing works
Origin of oligodendrocytes in the subventricular zone of the adult brain
Menn, B., Garcia-Verdugo, J. M., Yaschine, C., Gonzalez-Perez, O., Rowitch, D., & Alvarez-Buylla, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1299-06.2006 · Cited by 972 · see citing works
Eyes Wide Open: A Critical Review of Sphere-Formation as an Assay for Stem Cells
Pastrana, É., Silva-Vargas, V., & Doetsch, F. K. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.04.007 · Cited by 831 · see citing works
Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis
Shin, J., Berg, D. A., Zhu, Y., Shin, J. Y., Song, J., Bonaguidi, M. A., Enikolopov, G., Nauen, D. W., Christian, K. M., Ming, G.-L., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.07.013 · Cited by 784 · see citing works
Llorens-Bobadilla, E., Zhao, S., Baser, A., Saiz-Castro, G., Zwadlo, K., & Martin-Villalba, A. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.07.002 · Cited by 778 · see citing works
MEG3 noncoding RNA: a tumor suppressor
Zhou, Y., Zhang, X., & Klibanski, A. (2012) · Journal of Molecular Endocrinology · doi:10.1530/jme-12-0008 · Cited by 717 · see citing works
Codega, P., Silva-Vargas, V., Paul, A., Maldonado-Soto, A. R., DeLeo, A. M., Pastrana, E., & Doetsch, F. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.039 · Cited by 634 · see citing works
Frizzled and LRP5/6 Receptors for Wnt/ -Catenin SignalingPreprint
MacDonald, B. T., & He, X. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007880 · Cited by 610 · see citing works
Weigmann, A., Corbeil, D., Hellwig, A., & Huttner, W. Β. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12425 · Cited by 601 · see citing works
Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons
Habib, N., Li, Y., Heidenreich, M., Swiech, L., Avraham-Davidi, I., Trombetta, J. J., Hession, C., Zhang, F., & Regev, A. (2016) · Science · doi:10.1126/science.aad7038 · Cited by 601 · see citing works
Defective forebrain development in mice lacking gp330/megalin.
Willnow, T. E., Hilpert, J., Armstrong, S. A., Rohlmann, A., Hammer, R. E., Burns, D. K., & Herz, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8460 · Cited by 482 · see citing works
Self-citationCellular Taxonomy of the Mouse Striatum as Revealed by Single-Cell RNA-Seq
Gokce, O., Stanley, G. M., Treutlein, B., Neff, N. F., Camp, J. G., Malenka, R. C., Rothwell, P. E., Fuccillo, M. V., Südhof, T. C., & Quake, S. R. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.059 · Cited by 430 · see citing works
Single-Cell Transcriptomics Meets Lineage Tracing
Kester, L., & van Oudenaarden, A. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.014 · Cited by 375 · see citing works
Beckervordersandforth, R., Tripathi, P., Ninkovic, J., Bayam, E., Lepier, A., Stempfhuber, B., Kirchhoff, F., Hirrlinger, J., Haslinger, A., Lie, D. C., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.11.017 · Cited by 335 · see citing works
Dulken, B. W., Leeman, D. S., Boutet, S. C., Hebestreit, K., & Brunet, A. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.060 · Cited by 334 · see citing works
Kantarci, S., Al‐Gazali, L., Hill, R. S., Donnai, D., Black, G. C. M., Bieth, É., Chassaing, N., Lacombe, D., Devriendt, K., Teebi, A. S., et al. (2007) · Nature Genetics · doi:10.1038/ng2063 · Cited by 313 · see citing works
Qu, Q., Sun, G., Li, W., Su, Y., Ye, P., Zhao, C., Yu, R. T., Gage, F. H., Evans, R. M., & Shi, Y. (2009) · Nature Cell Biology · doi:10.1038/ncb2001 · Cited by 299 · see citing works
Dubreuil, V., Marzesco, A., Corbeil, D., Huttner, W. Β., & Wilsch‐Bräuninger, M. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200608137 · Cited by 292 · see citing works
Single-Cell Transcriptome Analyses Reveal Signals to Activate Dormant Neural Stem Cells
Luo, Y., Coskun, V., Liang, A., Yu, J., Cheng, L., Ge, W., Shi, Z., Zhang, K., Li, C., Cui, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.04.001 · Cited by 263 · see citing works
Ponti, G., Obernier, K., Guinto, C. D., Jose, L., Bonfanti, L., & Álvarez-Buylla, A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219563110 · Cited by 260 · see citing works
Artegiani, B., Lyubimova, A., Muraro, M., van Es, J. H., van Oudenaarden, A., & Clevers, H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.050 · Cited by 259 · see citing works
Adult Neurogenesis Is Sustained by Symmetric Self-Renewal and Differentiation
Obernier, K., Cebrian-Silla, A., Thomson, M., Parraguez, J. I., Anderson, R., Guinto, C., Rodas Rodriguez, J., Garcia-Verdugo, J.-M., & Alvarez-Buylla, A. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.01.003 · Cited by 250 · see citing works
A distinct population of microglia supports adult neurogenesis in the subventricular zone
Ribeiro Xavier, A. L., Kress, B. T., Goldman, S. A., Lacerda de Menezes, J. R., & Nedergaard, M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1217-15.2015 · Cited by 225 · see citing works
Shah, P. T., Stratton, J. A., Stykel, M. G., Abbasi, S., Sharma, S., Mayr, K. A., Koblinger, K., Whelan, P. J., & Biernaskie, J. (2018) · Cell · doi:10.1016/j.cell.2018.03.063 · Cited by 221 · see citing works
Cell fixation and preservation for droplet-based single-cell transcriptomics
Alles, J., Karaiskos, N., Praktiknjo, S. D., Grosswendt, S., Wahle, P., Ruffault, P.-L., Ayoub, S., Schreyer, L., Boltengagen, A., Birchmeier, C., et al. (2017) · BMC Biology · doi:10.1186/s12915-017-0383-5 · Cited by 218 · see citing works
Self-citationIt Takes a Village: Constructing the Neurogenic Niche
Bjornsson, C. S., Apostolopoulou, M., Tian, Y. I., & Temple, S. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.010 · Cited by 210 · see citing works
A mosaic world: puzzles revealed by adult neural stem cell heterogeneity
Chaker, Z., Codega, P., & Doetsch, F. (2016) · WIREs Developmental Biology · doi:10.1002/wdev.248 · Cited by 198 · see citing works
Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone
Calzolari, F., Michel, J., Baumgart, E. V., Theis, F. J., Götz, M., & Ninkovic, J. (2015) · Nature Neuroscience · doi:10.1038/nn.3963 · Cited by 186 · see citing works
Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy
Basak, O., Krieger, T. G., Muraro, M. J., Wiebrands, K., Stange, D. E., Frias-Aldeguer, J., Rivron, N. C., van de Wetering, M., van Es, J. H., van Oudenaarden, A., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715911114 · Cited by 186 · see citing works
LRP2/megalin is required for patterning of the ventral telencephalon
Spoelgen, R., Hammes, A., Anzenberger, U., Zechner, D., Andersen, O. M., Jerchow, B., & Willnow, T. E. (2004) · Development · doi:10.1242/dev.01580 · Cited by 175 · see citing works
Self-citationβ‐catenin signaling marks the prospective site of primitive streak formation in the mouse embryo
Mohamed, O. A., Clarke, H. J., & Dufort, D. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20135 · Cited by 174 · see citing works
LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic niche
Gajera, C. R., Emich, H., Lioubinski, O., Christ, A., Beckervordersandforth, R., Yoshikawa, K., Bachmann, S., Christensen, E., Götz, M., Kempermann, G., et al. (2010) · Journal of Cell Science · doi:10.1242/jcs.065912 · Cited by 153 · see citing works
Self-citationWalker, T., & Kempermann, G. (2014) · Journal of Visualized Experiments · doi:10.3791/51225 · Cited by 152 · see citing works
Paez-Gonzalez, P., Asrican, B., Rodriguez, E., & Kuo, C. T. (2014) · Nature Neuroscience · doi:10.1038/nn.3734 · Cited by 140 · see citing works
FACS purification of immunolabeled cell types from adult rat brain
Guez‐Barber, D., Fanous, S., Harvey, B. K., Zhang, Y., Lehrmann, E., Becker, K. G., Picciotto, M. R., & Hope, B. T. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2011.08.045 · Cited by 134 · see citing works
Zarbalis, K., May, S. R., Shen, Y., Ekker, M., Rubenstein, J. L. R., & Peterson, A. S. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020219 · Cited by 130 · see citing works
Christ, A., Christa, A., Kur, E., Lioubinski, O., Bachmann, S., Willnow, T. E., & Hammes, A. (2012) · Developmental Cell · doi:10.1016/j.devcel.2011.11.023 · Cited by 120 · see citing works
Self-citationProspective isolation of adult neural stem cells from the mouse subependymal zone
Fischer, J., Beckervordersandforth, R., Tripathi, P., Steiner-Mezzadri, A., Ninkovic, J., & Götz, M. (2011) · Nature Protocols · doi:10.1038/nprot.2011.412 · Cited by 71 · see citing works
LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic Stimuli
Christ, A., Christa, A., Klippert, J., Eule, J. C., Bachmann, S., Wallace, V. A., Hammes, A., & Willnow, T. E. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.09.001 · Cited by 57 · see citing works
Self-citationDiversity of Neural Precursors in the Adult Mammalian BrainPreprint
Bonaguidi, M. A., Stadel, R. P., Berg, D. A., Sun, J., Ming, G., & Song, H. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018838 · Cited by 50 · see citing works
LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease
Christ, A., Herzog, K., & Willnow, T. E. (2016) · Developmental Dynamics · doi:10.1002/dvdy.24394 · Cited by 48 · see citing works
Self-citationEndocytic receptor LRP2/megalin—of holoprosencephaly and renal Fanconi syndrome
Willnow, T. E., & Christ, A. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1992-0 · Cited by 48 · see citing works
Self-citationWalker, T. L., & Kempermann, G. (2014) · Journal of Visualized Experiments · doi:10.3791/51225-v · Cited by 44 · see citing works
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Ximerakis, M., Lipnick, S. L., Innes, B. T., Simmons, S. K., Adiconis, X., Dionne, D., Mayweather, B. A., Nguyen, L., Niziolek, Z., Ozek, C., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0491-3 · Cited by 736 · see citing works
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La Manno, G., Siletti, K., Furlan, A., Gyllborg, D., Vinsland, E., Mossi Albiach, A., Mattsson Langseth, C., Khven, I., Lederer, A. R., Dratva, L. M., et al. (2021) · Nature · doi:10.1038/s41586-021-03775-x · Cited by 563 · see citing works
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Dulken, B. W., Buckley, M. T., Navarro Negredo, P., Saligrama, N., Cayrol, R., Leeman, D. S., George, B. M., Boutet, S. C., Hebestreit, K., Pluvinage, J. V., et al. (2019) · Nature · doi:10.1038/s41586-019-1362-5 · Cited by 521 · see citing works
Marsh, S. E., Walker, A. J., Kamath, T., Dissing-Olesen, L., Hammond, T. R., de Soysa, T. Y., Young, A. M. H., Murphy, S., Abdulraouf, A., Nadaf, N., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01022-8 · Cited by 432 · see citing works
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Piwecka, M., Rajewsky, N., & Rybak-Wolf, A. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00809-y · Cited by 320 · see citing works
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Gazestani, V., Kamath, T., Nadaf, N. M., Dougalis, A., Burris, S. J., Rooney, B., Junkkari, A., Vanderburg, C., Pelkonen, A., Gomez-Budia, M., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.005 · Cited by 209 · see citing works
Kaiser, K., Gyllborg, D., Procházka, J., Salašová, A., Kompaníková, P., Molina, F. L., Laguna-Goya, R., Radaszkiewicz, T., Harnoš, J., Procházková, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09298-4 · Cited by 87 · see citing works
Xu, B., Li, Q., Wu, Y., Wang, H., Xu, J., Liu, H., & Xuan, A. (2022) · The FASEB Journal · doi:10.1096/fj.202200133rr · Cited by 35 · see citing works
- Authors
- Zywitza, V., Misios, A., Bunatyan, L., Willnow, T. E., & Rajewsky, N.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Willnow, Thomas E.
- Rajewsky, Nikolaus
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 25
- Issue
- 9
- Pages
- 2457-2469.e8
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2813292791
- Cited by
- 183
- References
- 60
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 16 · 2023: 30 · 2022: 32 · 2021: 22 · 2020: 37 · 2019: 20 · 2018: 1
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- SSRN Electronic Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- European Union
- Marie Sklodowska-Curie Actions (721890)
- Chan Zuckerberg Initiative
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- subventricular zone, adult neurogenesis, neural stem cells, cell types, cell atlas, RNA kinetics, Wnt signaling, BMP signaling, megalin, endocytic receptor, stem cell niche, progenitor cell proliferation
- MeSH terms
- Aging, Animals, Gene Expression Regulation, Mice, Inbred C57BL, Models, Biological, RNA, Dentate Gyrus, Cell Lineage, Lateral Ventricles, Low Density Lipoprotein Receptor-Related Protein-2, Cell Proliferation, Stem Cell Niche, Neurogenesis, Neural Stem Cells, Single-Cell Analysis, Transcriptome, RNA, Long Noncoding
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