The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Cell-type-specific metabolic labeling of nascent proteomes in vivo
Abstract
Although advances in protein labeling methods have made it possible to measure the proteome of mixed cell populations, it has not been possible to isolate cell-type-specific proteomes in vivo. This is because the existing methods for metabolic protein labeling in vivo access all cell types. We report the development of a transgenic mouse line where Cre-recombinase-induced expression of a mutant methionyl-tRNA synthetase (L274G) enables the cell-type-specific labeling of nascent proteins with a non-canonical amino-acid and click chemistry. Using immunoblotting, imaging and mass spectrometry, we use our transgenic mouse to label and analyze proteins in excitatory principal neurons and Purkinje neurons in vitro (brain slices) and in vivo. We discover more than 200 proteins that are differentially regulated in hippocampal excitatory neurons by exposing mice to an environment with enriched sensory cues. Our approach can be used to isolate, analyze and quantitate cell-type-specific proteomes and their dynamics in healthy and diseased tissues.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Several key proteins (e.g., APP, Grm5) linked to neurodevelopmental or neurodegenerative disorders were also identified [158].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
In the citing paper
“Proteins within a specific cell type can be uniquely labeled in vivo via BONCAT (Fig. 2) and isolated from a complex tissue, such as the brain, for MS-based proteomics.”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
In the citing paper
“The Camk2a hippocampal proteome was significantly enriched with proteins represented by neuronal components, such as synaptic transmission and synaptic plasticity.”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
In the citing paper
“Recently, BONCAT was utilized to characterize excitatory and inhibitory neuronal proteomes in adult mice [158, 159].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [158]
Citations
Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
The Perseus computational platform for comprehensive analysis of (prote)omics data
Tyanova, S., Temu, T., Sinitcyn, P., Carlson, A., Hein, M. Y., Geiger, T., Mann, M., & Cox, J. (2016) · Nature Methods · doi:10.1038/nmeth.3901 · Cited by 8,803
Universal sample preparation method for proteome analysis
Wiśniewski, J. R., Zougman, A., Nagaraj, N., & Mann, M. (2009) · Nature Methods · doi:10.1038/nmeth.1322 · Cited by 8,352
The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat
O'Keefe, J., & Dostrovsky, J. (1971) · Brain Research · doi:10.1016/0006-8993(71)90358-1 · Cited by 6,151
Ong, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356
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
A simple method for organotypic cultures of nervous tissue
Stoppini, L., Buchs, P., & Muller, D. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90128-m · Cited by 3,096
ProteomeXchange provides globally coordinated proteomics data submission and dissemination
Vizcaíno, J. A., Deutsch, E. W., Wang, R., Csordás, A., Reisinger, F., Ríos, D., Dianes, J. A., Sun, Z., Farrah, T., Bandeira, N., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2839 · Cited by 2,735
Place Cells, Grid Cells, and the Brain's Spatial Representation System
Moser, E. I., Kropff, E., & Moser, M.-B. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.061307.090723 · Cited by 1,934
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–220 of 220
The proteasome maturation factor POMP moonlights as a stress-induced transcriptional regulatorPreprint
Giandomenico, S. L., Mueller, M. P., van Oostrum, M., Desch, K., Krause, B., Tushev, G., Ciirdaeva, E., Langer, J. D., Alvarez‐Castelao, B., & Schuman, E. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.25.650603 · Cited by 1
Self-citation10 Protein Modification through Metabolic Incorporation of Noncanonical Amino Acids
Ignacio, B. J., Leirs, H., van der Zanden, N., & Bonger, K. M. (2025) · Haug Verlag in Georg Thieme Verlag KG eBooks · doi:10.1055/sos-sd-242-00165
Mitochondria remodel near synapses to boost metabolic capacity and fuel plasticityPreprint
Shah, M., Ghosh, I., Ramesh, N. S., Pishos, L., Pancani, T., Villani, V., Yasuda, R., Loomba, S., Sun, C., Kamasawa, N., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.27.672715 · Cited by 1
Omachi, K., & Fujiwara, H. (2025) · Matrix Biology · doi:10.1016/j.matbio.2025.09.001
Hibbert, J. E., Jorgenson, K. W., Sayed, R. K. A., Paez, H. G., Meinhold, M., Flynn, C. G. K., Lange, A. N., Lindley, G. T., Flejsierowicz, P. M., & Hornberger, T. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.19.676647
Burgess, J. D., Amerna, D., Norton, E. S., Parsons, T. M., Perkerson, R. B., Faroqi, A. H., Wszolek, Z. K., Guerrero‐Cazares, H., Kanekiyo, T., Delenclos, M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24257443
Burgess, J. D., Amerna, D., Norton, E. S., Parsons, T. M., Perkerson, R. B., Faroqi, A. H., Wszolek, Z. K., Guerrero‐Cazares, H., Kanekiyo, T., Delenclos, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24257637
Burgess, J. D., Amerna, D., Norton, E. S., Parsons, T. M., Perkerson, R. B., Faroqi, A. H., Wszolek, Z. K., Guerrero‐Cazares, H., Kanekiyo, T., Delenclos, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26623549
Burgess, J. D., Amerna, D., Norton, E. S., Parsons, T. M., Perkerson, R. B., Faroqi, A. H., Wszolek, Z. K., Guerrero‐Cazares, H., Kanekiyo, T., Delenclos, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26623552
Sridharan, D., Dougherty, J. A., Ahmed, U., Sanghvi, S. K., Alvi, S. B., Park, K. H., Islam, H., Knoblaugh, S. E., Singh, H., Kirby, E. D., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26739513
Burgess, J. D., Amerna, D., Norton, E. S., Parsons, T. M., Perkerson, R. B., Faroqi, A. H., Wszolek, Z. K., Guerrero‐Cazares, H., Kanekiyo, T., Delenclos, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26623546
Hinds, G. K., Velieva, A. E., Liu, Y., Roy, A., Chavali, R., & Loebel, C. (2026) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbma.70038
Click Chemistry for Protein Modification in Live Cells and In Vivo
Sakamoto, S., & Hamachi, I. (2026) · Topics in heterocyclic chemistry · doi:10.1007/7081_2025_102
From brown to white: Brown adipose tissue endothelial cells whiten in culture conditions
Elschner, T., Grein, S., Sander, J., Hildebrand, S., Heubach, L., Pannwitz, N., Mircea, M., Raimundez, E., Karagiannakou, V., Georgiadi, A., et al. (2026) · Molecular Metabolism · doi:10.1016/j.molmet.2026.102349
Chemical biology tools for studying tissue development
Zhang, M., & Han, S. (2026) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2026.103679
Astrocytes viewed through the lens of their proteomes and subproteomes
Casha, V. H., Wu, L., Wohlschlegel, J. A., & Khakh, B. S. (2026) · Nature reviews. Neuroscience · doi:10.1038/s41583-026-01054-0 · Cited by 1
Mitochondrial turnover at central GABAergic synapses governs vulnerability to epileptic seizuresPreprint
Ndoci, K., Chihab, A. W., Ganesan, K., Jevtic, M., Tofan, K. M., Wani, G. A., Pelzer, P., Soriano-Campos, J. A., Odenthal, F., Sakthivelu, V., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.24.734182
Domain-specific proteome remodeling defines mouse myelin agingPreprint
Freund, Y., Schoof, M., Moreno, N., Kriegel, F., Shin, H., Waelchli, V., Kaur, A., Abraham, K., Fogel, I., Shi, S. M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.05.736479 · Cited by 1
Testing cellular provenance in the cancer extracellular matrix
Ma, M., Huang, Y., Tang, E., Zhang, Y., Yang, X., Huang, L., & Ma, H. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1984128
Bioorthogonal Chemistry in Neurobiology: From Imaging to Proteomics
Taylor, N. C., de Sousa-Lourenço, J., & Nikić, I. (2026) · ChemBioChem · doi:10.1002/cbic.202500949
Metadata
- Authors
- Alvarez-Castelao, B., Schanzenbächer, C. T., Hanus, C., Glock, C., tom Dieck, S., Dörrbaum, A. R., Bartnik, I., Nassim-Assir, B., Ciirdaeva, E., Mueller, A., Dieterich, D. C., Tirrell, D. A., Langer, J. D., & Schuman, E. M.
- Affiliations
- Max Planck Institute of Biophysics (DE)
- Max Planck Institute for Brain Research (DE)
- Center for Behavioral Brain Sciences (DE)
- California Institute of Technology (US)
- Corresponding author
- Schuman, Erin M
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2017-11-06
- Volume
- 35
- Issue
- 12
- Pages
- 1196-1201
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2765371514
- Semantic Scholar
- 2688eacdb4dbfc63c3da8b32bdde84e7bfbfaea1
- Cited by
- 219
- References
- 50
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 40 · 2023: 27 · 2022: 25 · 2021: 19 · 2020: 26 · 2019: 17 · 2018: 17 · 2017: 2
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-16-CE16-0009)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Keywords
- click chemistry, transgenic mice, Cre recombinase, Purkinje cells, hippocampus
- MeSH terms
- Amino Acids, Animals, Female, Gene Expression Regulation, Male, Methionine-tRNA Ligase, Mice, Transgenic, Neurons, Integrases, Proteome, Proteomics, Mice, Click Chemistry
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
