Bayesian sparse regression analysis documents the diversity of spinal inhibitory interneurons
Open accessAbstract
Documenting the extent of cellular diversity is a critical step in defining the functional organization of tissues and organs. To infer cell-type diversity from partial or incomplete transcription factor expression data, we devised a sparse Bayesian framework that is able to handle estimation uncertainty and can incorporate diverse cellular characteristics to optimize experimental design. Focusing on spinal V1 inhibitory interneurons, for which the spatial expression of 19 transcription factors has been mapped, we infer the existence of ~50 candidate V1 neuronal types, many of which localize in compact spatial domains in the ventral spinal cord. We have validated the existence of inferred cell types by direct experimental measurement, establishing this Bayesian framework as an effective platform for cell-type characterization in the nervous system and elsewhere.
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Combinatorial expression of 19 TFs has been proposed to generate multiple subpopulations of V1 interneurons.
“Moreover, the combinatorial expression of 19 TFs have been proposed to generate multiple subpopulations of V1 interneurons (Bikoff et al., 2016; Gabitto et al., 2016; Sweeney et al., 2018).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Gabitto et al., 2016
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Gelman, A., Carlin, J. B., Stern, H. S., Dunson, D. B., Vehtari, A., & Rubin, D. B. (2013) · doi:10.1201/b16018 · Cited by 27,276 · 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
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195 · see citing works
Correlation between Protein and mRNA Abundance in Yeast
Gygi, S. P., Rochon, Y., Franza, B. R., & Aebersold, R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1720 · Cited by 3,819 · see citing works
Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells
Klein, A. M., Mazutis, L., Akartuna, I., Tallapragada, N., Veres, A., Li, V., Peshkin, L., Weitz, D. A., & Kirschner, M. W. (2015) · Cell · doi:10.1016/j.cell.2015.04.044 · Cited by 3,356 · see citing works
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124 · see citing works
Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing
Usoskin, D., Furlan, A., Islam, S., Abdo, H., Lönnerberg, P., Lou, D., Hjerling-Leffler, J., Haeggström, J., Kharchenko, O., Kharchenko, P. V., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3881 · Cited by 2,136 · see citing works
Adult mouse cortical cell taxonomy revealed by single cell transcriptomics
Tasic, B., Menon, V., Nguyen, T. N., Kim, T. K., Jarsky, T., Yao, Z., Levi, B., Gray, L. T., Sorensen, S. A., Dolbeare, T., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4216 · Cited by 1,714 · see citing works
How Inhibition Shapes Cortical Activity
Isaacson, J. S., & Scanziani, M. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.027 · Cited by 1,678 · see citing works
Interneuron cell types are fit to function
Kepecs, A., & Fishell, G. (2014) · Nature · doi:10.1038/nature12983 · Cited by 1,110 · see citing works
Spike and slab variable selection: Frequentist and Bayesian strategies
Ishwaran, H., & Rao, J. S. (2005) · The Annals of Statistics · doi:10.1214/009053604000001147 · Cited by 1,031 · see citing works
Cell type- and brain region-resolved mouse brain proteome
Sharma, K., Schmitt, S., Bergner, C. G., Tyanova, S., Kannaiyan, N., Manrique-Hoyos, N., Kongi, K., Cantuti, L., Hanisch, U.-K., Philips, M.-A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4160 · Cited by 871 · see citing works
Molecular logic of neocortical projection neuron specification, development and diversity
Greig, L. C., Woodworth, M. B., Galazo, M. J., Padmanabhan, H., & Macklis, J. D. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3586 · Cited by 863 · see citing works
New insights into the classification and nomenclature of cortical GABAergic interneurons
DeFelipe, J., López-Cruz, P. L., Benavides-Piccione, R., Bielza, C., Larrañaga, P., Anderson, S., Burkhalter, A., Cauli, B., Fairén, A., Feldmeyer, D., et al. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3444 · Cited by 833 · see citing works
The Types of Retinal Ganglion Cells: Current Status and Implications for Neuronal Classification
Sanes, J. R., & Masland, R. H. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-034120 · Cited by 789 · see citing works
Activity-dependent regulation of inhibitory synapse development by Npas4
Lin, Y., Bloodgood, B. L., Hauser, J. L., Lapan, A. D., Koon, A. C., Kim, T.-K., Hu, L. S., Malik, A. N., & Greenberg, M. E. (2008) · Nature · doi:10.1038/nature07319 · Cited by 639 · see citing works
Precise Localization of Renshaw Cells with a New Marking Technique
THOMAS, R. C., & Wilson, V. J. (1965) · Nature · doi:10.1038/206211b0 · Cited by 470 · see citing works
A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity
Dasen, J. S., Tice, B. C., Brenner-Morton, S., & Jessell, T. M. (2005) · Cell · doi:10.1016/j.cell.2005.09.009 · Cited by 461 · see citing works
Self-citationCENTRAL EFFECTS OF CENTRIPETAL IMPULSES IN AXONS OF SPINAL VENTRAL ROOTS
Renshaw, B. (1946) · Journal of Neurophysiology · doi:10.1152/jn.1946.9.3.191 · Cited by 445 · see citing works
Abbas, A. R., Wolslegel, K., Seshasayee, D., Modrusan, Z. D., & Clark, H. F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006098 · Cited by 418 · see citing works
Temporal fate specification and neural progenitor competence during development
Kohwi, M., & Doe, C. Q. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3618 · Cited by 366 · see citing works
Recurrent inhibition of interneurones monosynaptically activated from group Ia afferents
Hultborn, H., Jankowska, E., & Lindström, S. (1971) · The Journal of Physiology · doi:10.1113/jphysiol.1971.sp009488 · Cited by 326 · see citing works
Chapter Six Hox Networks and the Origins of Motor Neuron Diversity
Dasen, J. S., & Jessell, T. M. (2009) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(09)88006-x · Cited by 309 · see citing works
Self-citationComputational deconvolution: extracting cell type-specific information from heterogeneous samples
Shen-Orr, S. S., & Gaujoux, R. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.09.015 · Cited by 280 · see citing works
Spinal inhibitory interneuron diversity delineates variant motor microcircuits
Bikoff, J. B., Gabitto, M. I., Rivard, A. F., Drobac, E., Machado, T. A., Miri, A., Brenner-Morton, S., Famojure, E., Diaz, C., Alvarez, F. J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.01.027 · Cited by 262 · see citing works
Postnatal phenotype and localization of spinal cord V1 derived interneurons
Alvarez, F. J., Jonas, P. C., Sapir, T., Hartley, R., Berrocal, M. C., Geiman, E. J., Todd, A. J., & Goulding, M. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20711 · Cited by 243 · see citing works
Zhang, J., Lanuza, G. M., Britz, O., Wang, Z., Siembab, V. C., Zhang, Y., Velasquez, T., Alvarez, F. J., Frank, E., & Goulding, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.013 · Cited by 233 · see citing works
Digital sorting of complex tissues for cell type-specific gene expression profiles
田中, 義., Wan, Y., Pang, K., Chow, L. M. L., & Liu, Z. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-89 · Cited by 207 · see citing works
Exact Hamiltonian Monte Carlo for Truncated Multivariate Gaussians
Pakman, A., & Paninski, L. (2013) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.2013.788448 · Cited by 194 · see citing works
Self-citationPax6 and Engrailed 1 Regulate Two Distinct Aspects of Renshaw Cell Development
Sapir, T., Geiman, E. J., Wang, Z., Velasquez, T., Mitsui, S., Yoshihara, Y., Frank, E., Álvarez, F. J., & Goulding, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3187-03.2004 · Cited by 189 · see citing works
Saueressig, H., Burrill, J. D., & Goulding, M. (1999) · Development · doi:10.1242/dev.126.19.4201 · Cited by 188 · see citing works
Genetic address book for retinal cell types
Siegert, S., Scherf, B. G., Del Punta, K., Didkovsky, N., Heintz, N., & Roska, B. (2009) · Nature Neuroscience · doi:10.1038/nn.2370 · Cited by 188 · see citing works
The continuing case for the Renshaw cell
Álvarez, F. J., & Fyffe, R. E. W. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.136200 · Cited by 171 · see citing works
Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch
Dehorter, N., Ciceri, G., Bartolini, G., Lim, L., del Pino, I., & Marín, O. (2015) · Science · doi:10.1126/science.aab3415 · Cited by 169 · see citing works
Gong, T., Hartmann, N., Kohane, I. S., Brinkmann, V., Staedtler, F., Letzkus, M., Bongiovanni, S., & Szustakowski, J. D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027156 · Cited by 147 · see citing works
Semi-supervised Nonnegative Matrix Factorization for gene expression deconvolution: A case study
Gaujoux, R., & Seoighe, C. (2011) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2011.08.014 · Cited by 127 · see citing works
Biomarker discovery in heterogeneous tissue samples -taking the in-silico deconfounding approach
Repsilber, D., Kern, S., Telaar, A., Walzl, G., Black, G. F., Selbig, J., Parida, S. K., Kaufmann, S. H. E., & Jacobsen, M. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-27 · Cited by 118 · see citing works
Stam, F. J., Hendricks, T. J., Zhang, J., Geiman, E. J., Francius, C., Labosky, P. A., Clotman, F., & Goulding, M. (2012) · Development · doi:10.1242/dev.071134 · Cited by 115 · see citing works
Transcriptional mechanisms controlling motor neuron diversity and connectivity
di Sanguinetto, S. D. T., Dasen, J. S., & Arber, S. (2008) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2008.04.002 · Cited by 109 · see citing works
García, N. V. D. M., & Jessell, T. M. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.033 · Cited by 103 · see citing works
Self-citationTowards the automatic classification of neurons
Armañanzas, R., & Ascoli, G. A. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.02.004 · Cited by 102 · see citing works
Development-Inspired Reprogramming of the Mammalian Central Nervous System
Amamoto, R., & Arlotta, P. (2014) · Science · doi:10.1126/science.1239882 · Cited by 101 · see citing works
Benito‐Gonzalez, A., & Álvarez, F. J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3630-12.2012 · Cited by 91 · see citing works
Liebner, D. A., Huang, K., & Parvin, J. D. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt566 · Cited by 88 · see citing works
Probabilistic analysis of gene expression measurements from heterogeneous tissues
Erkkilä, T., Lehmusvaara, S., Ruusuvuori, P., Visakorpi, T., Ilya Shmulevich, C., & Lähdesmäki, H. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq406 · Cited by 88 · see citing works
Computational expression deconvolution in a complex mammalian organ
Wang, M., Master, S. R., & Chodosh, L. A. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-328 · Cited by 83 · see citing works
New dimensions of interneuronal specialization unmasked by principal cell heterogeneity
Krook-Magnuson, E., Varga, C., Lee, S.-H., & Soltesz, I. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.10.005 · Cited by 63 · see citing works
Cell-type–based model explaining coexpression patterns of genes in the brain
Grange, P., Bohland, J. W., Okaty, B. W., Sugino, K., Bokil, H., Nelson, S. B., Ng, L., Hawrylycz, M., & Mitra, P. P. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312098111 · Cited by 61 · see citing works
ASSIGN: context-specific genomic profiling of multiple heterogeneous biological pathways
Shen, Y., Roosan, M. R., Piccolo, S., et al. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv031 · Cited by 46 · see citing works
Evidence for separate morphological classes of Renshaw cells in the cat's spinal cord
Fyffe, R. E. W. (1990) · Brain Research · doi:10.1016/0006-8993(90)90038-d · Cited by 45 · see citing works
Auxiliary-variable Exact Hamiltonian Monte Carlo Samplers for Binary DistributionsPreprint
Pakman, A., & Paninski, L. (2013) · arXiv (Cornell University) · doi:10.48550/arxiv.1311.2166 · Cited by 38 · see citing works
Self-citationNeuroinformatics Grand Challenges
Ascoli, G. A. (2008) · Neuroinformatics · doi:10.1007/s12021-008-9010-5 · Cited by 33 · see citing works
Molecular development and repair of corticospinal motor neuron circuitry
Molyneaux, B. J., Arlotta, P., & Macklis, J. D. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.02.074 · Cited by 29 · see citing works
Molecular Development of Corticospinal Motor Neuron Circuitry
Molyneaux, B. J., Arlotta, P., & Macklis, J. D. (2008) · Novartis Foundation symposium · doi:10.1002/9780470994030.ch2 · Cited by 25 · see citing works
Augen, J. (2004) · CERN Document Server (European Organization for Nuclear Research) · Cited by 24 · see citing works
Unsupervised Bayesian linear unmixing of gene expression microarrays
Bazot, C., Dobigeon, N., Tourneret, J., et al. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-99 · Cited by 15 · see citing works
Zuk, O., Amir, A., Zeisel, A., et al. (2013) · Lecture notes in computer science · doi:10.1007/978-3-319-02432-5_31 · Cited by 4 · see citing works
Sensory-Motor Circuits: Hox Genes Get in Touch
Philippidou, P., & Dasen, J. S. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.035 · Cited by 3 · see citing works
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- Authors
- Gabitto, M. I., Pakman, A., Bikoff, J. B., Abbott, L. F., Jessell, T. M., & Paninski, L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Columbia University (US)
- Corresponding author
- Gabitto, Mariano I.
- Paninski, Liam
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 165
- Issue
- 1
- Pages
- 220-233
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4831714
- OpenAlex
- W2289759715
- Cited by
- 73
- References
- 59
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 6 · 2019: 11 · 2018: 10 · 2017: 7 · 2016: 5
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- NIH (NS033245, MH093338)
- Harold and Leila Y. Mathers Foundation
- Brain Research Foundation
- Gatsby
- Swartz
- Mathers Foundations
- ONR (N00014-14-1-0243)
- ARO MURI (W911NF-12-1-0594)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- cell type diversity, sparse Bayesian inference, transcription factor expression, ventral spinal cord, estimation uncertainty, experimental design optimization, neuronal cell types
- MeSH terms
- Animals, Bayes Theorem, Spinal Cord, Transcription Factors, Mice, Transcriptome, Renshaw Cells
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