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Genome-wide atlas of gene expression in the adult mouse brain
Abstract
Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.
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“In order to independently validate our findings about the spatial distribution of astrocytes (Figure S5C), we analyzed in situ hybridization images of marker genes obtained from the Allen Mouse Brain Atlas”
From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Lein et al., 2007
In the citing paper
“Allen Brain Atlas in situ hybridization data [24] show ATF3 expression only in granular neurons of the olfactory bulb and dentate gyrus”
From Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis (2015) · cites this paper as [24]
In the citing paper
“Further in situ hybridization reveals that cerebellar Purkinje cells and neurons of the deep cerebellar nuclei express high levels of Clec16a (Allen Mouse Brain Atlas, http://mouse.brain-map.org/gene/show/50215)242526.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [24]
In the citing paper
“we analyzed Nlk expression by LacZ staining and found that LacZ staining was strongest in the Purkinje cell layer (Fig.4D)”
From Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1 (2013) · cites this paper as Lein et al., 2007
In the citing paper
“In animal studies (rodents and non-human primates), this is feasible through the use of comprehensive, histologically and functionally defined whole-brain areal parcellations (Bezgin et al., 2012; Lein et al., 2007; Paxinos et al., 2000; Saleem and Logothetis, 2007; Swanson, 2015; Van Essen et al., 2012).”
From Development of large-scale functional networks from birth to adulthood: A guide to the neuroimaging literature (2017) · cites this paper as Lein et al., 2007
In the citing paper
“ApoE expression, in both mice and humans, begins relatively late in development [46, 47].”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [47]
In the citing paper
“To complement and validate the microarray data, several targeted, large-scale in situ hybridization (ISH) data sets were generated using a high-throughput ISH platform1, 8.”
From An anatomically comprehensive atlas of the adult human brain transcriptome (2012) · cites this paper as [1]
In the citing paper
“In rodents, brain- and transcriptome-wide, cellular-resolution maps of transcript distributions are widely useful resources to complement genomic sequence data1, 2, 3.”
From An anatomically comprehensive atlas of the adult human brain transcriptome (2012) · cites this paper as [1]
In the citing paper
“consistent with the percentage of genes expressed in mouse brain by ISH (80%; ref. 1) and fetal human brain by microarrays (76%; ref. 11).”
From An anatomically comprehensive atlas of the adult human brain transcriptome (2012) · cites this paper as [1]
In the citing paper
“expression in human differs from that in mouse (Fig. 5d) and rhesus monkey (Fig. 5e), where CALB1 is robustly expressed in CA1 and CA2 in addition to dentate gyrus.”
From An anatomically comprehensive atlas of the adult human brain transcriptome (2012) · cites this paper as [1]
In the citing paper
“The atlas of the mid-gestational human brain described here, part of the BrainSpan Atlas of the Developing Human Brain, builds on digital molecular brain atlasing efforts in mouse20,22,24 and adult human23 by providing transcriptome resources on prenatal specimens typically inaccessible for research.”
From Transcriptional landscape of the prenatal human brain (2014) · cites this paper as [24]
In the citing paper
“These cell-type-specific expression patterns exhibited specific anatomical localization in the developing cerebellum (Fig. 1c) 26 .”
From Single-cell isoform RNA sequencing characterizes isoforms in thousands of cerebellar cells (2018) · cites this paper as [26]
In the citing paper
“The distribution of specific markers ( Pcp4 and Slc17a7 ) captured by Stereo-seq exhibited the expected similarity to in situ hybridization (ISH) data taken from Allen Brain Atlas (ABA) (Lein et al., 2007) and clearer patterns than HDST (Vickovic et al., 2019) or Slide-seqV2-resolved (Stickels et al., 2021) expression data (Figure S1E).”
From Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays (2022) · cites this paper as Lein et al., 2007
In the citing paper
“The expression patterns of Hes1 and Hes5 are consistent with ISH images taken from ABA (Figure S7H) (Lein et al., 2007).”
From Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays (2022) · cites this paper as Lein et al., 2007
In the citing paper
“These results are in line with ISH images of the Rspo1 and Fgf15 taken from ABA (Lein et al., 2007) (Figure S7F).”
From Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays (2022) · cites this paper as Lein et al., 2007
In the citing paper
“The expression patterns of Erbb4 and Gad2 are consistent with ISH images taken from ABA (Lein et al., 2007) (Figure S6F).”
From Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays (2022) · cites this paper as Lein et al., 2007
In the citing paper
“Finally, we compared all marker genes that we highlight in this paper (those in Table 1 and all figures) to their patterns in a recent spatial transcriptomics analysis of the spinal cord28 and to the Allen29 and Gensat30 expression databases and found general concordance between these resources (Supplementary Table 4).”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [29]
In the citing paper
“Initial clustering identified 106,728 neurons, of which 70.2% were localized to BNST by examination of marker expression in the Allen Brain Atlas (ABA) (Lein et al., 2007) (Figure S3B).”
From Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity (2019) · cites this paper as Lein et al., 2007
In the citing paper
“In situ hybridization and microarray data, for example the Allen Brain Atlases (Hawrylycz et al., 2012; Lein et al., 2007), have also established that mRNA transcripts encoding these five NPPs and that many other NPPs and NP-GPCR genes are expressed differentially in many brain regions.”
From Single-cell transcriptomic evidence for dense intracortical neuropeptide networks (2019) · cites this paper as Lein et al., 2007
In the citing paper
“Inspection of ISHs from the Allen Brain Atlas (Lein et al., 2007) indicated that these neurons were located in the Edinger-Westphal nucleus, which is adjacent to the DRN, confirming that our dissection region spanned most of the DRN along the anterior-posterior axis.”
From Molecular and anatomical organization of the dorsal raphe nucleus (2019) · cites this paper as Lein et al., 2007
In the citing paper
“We leveraged the inclusion of adjacent brain tissue in our atlas to map the boundary between the 3V ChP and developing pineal gland using published ISH (Lein et al., 2007; Visel et al., 2004) of marker genes from our data (Figure S2C).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Lein et al., 2007
In the citing paper
“Signature scores were distinctly elevated in areas corresponding to the anatomical structures annotated in the Allen brain reference atlas (Figure S3A) (Lein et al., 2007).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Lein et al., 2007
In the citing paper
“We compared the expression of marker genes to insitu hybridization (ISH) data from the Allen Mouse Brain Atlas(Lein et al., 2007) and visual landmarks from the H&E microscopy images”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Lein et al., 2007
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Metadata
- Authors
- 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., Chen, L., Chen, L., Chen, T.-M., Chi Chin, M., Chong, J., Crook, B. E., Czaplinska, A., Dang, C. N., Datta, S., Dee, N. R., Desaki, A. L., Desta, T., Diep, E., Dolbeare, T. A., Donelan, M. J., Dong, H.-W., Dougherty, J. G., Duncan, B. J., Ebbert, A. J., Eichele, G., Estin, L. K., Faber, C., Facer, B. A., Fields, R., Fischer, S. R., Fliss, T. P., Frensley, C., Gates, S. N., Glattfelder, K. J., Halverson, K. R., Hart, M. R., Hohmann, J. G., Howell, M. P., Jeung, D. P., Johnson, R. A., Karr, P. T., Kawal, R., Kidney, J. M., Knapik, R. H., Kuan, C. L., Lake, J. H., Laramee, A. R., Larsen, K. D., Lau, C., Lemon, T. A., Liang, A. J., Liu, Y., Luong, L. T., Michaels, J., Morgan, J. J., Morgan, R. J., Mortrud, M. T., Mosqueda, N. F., Ng, L. L., Ng, R., Orta, G. J., Overly, C. C., Pak, T. H., Parry, S. E., Pathak, S. D., Pearson, O. C., Puchalski, R. B., Riley, Z. L., Rockett, H. R., Rowland, S. A., Royall, J. J., Ruiz, M. J., Sarno, N. R., Schaffnit, K., Shapovalova, N. V., Sivisay, T., Slaughterbeck, C. R., Smith, S. C., Smith, K. A., Smith, B. I., Sodt, A. J., Stewart, N. N., Stumpf, K.-R., Sunkin, S. M., Sutram, M., Tam, A., Teemer, C. D., Thaller, C., Thompson, C. L., Varnam, L. R., Visel, A., Whitlock, R. M., Wohnoutka, P. E., Wolkey, C. K., Wong, V. Y., Wood, M., Yaylaoglu, M. B., Young, R. C., Youngstrom, B. L., Feng Yuan, X., Zhang, B., Zwingman, T. A., & Jones, A. R.
- Affiliations
- Allen Institute for Brain Science (US)
- Baylor College of Medicine (US)
- Novartis (Switzerland) (CH)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Lein, Ed S.
- Jones, Allan R.
- ORCID
- Lein, Ed S.
- Hawrylycz, Michael J.
- Bernard, Amy
- Chen, Lin
- Chong, Jimmy
- Dee, Nick R.
- Desta, Tsega
- Dolbeare, Tim A.
- Dong, Hong-Wei
- Fliss, Tim P.
- Glattfelder, Katie J.
- Hart, Matthew R.
- Hohmann, John G.
- Liu, Ying
- Ng, Lydia L.
- Puchalski, Ralph B.
- Shapovalova, Nadiya V.
- Smith, Kimberly A.
- Sunkin, Susan M.
- Thompson, Carol L.
- Visel, Axel
- Wohnoutka, Paul E.
- Wood, Matthew
- Zhang, Bin
- Zwingman, Theresa A.
- Jones, Allan R.
- Venue
- Nature
- Published
- 2006-12-06
- Volume
- 445
- Issue
- 7124
- Pages
- 168-176
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2123491442
- Cited by
- 5,572
- References
- 58
- Citations by year
- 2026: 237 · 2025: 327 · 2024: 368 · 2023: 347 · 2022: 409 · 2021: 435 · 2020: 398 · 2019: 342 · 2018: 320 · 2017: 296 · 2016: 280 · 2015: 236 · 2014: 252 · 2013: 203 · 2012: 223
- FWCI
- 68.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- gene expression atlas, mouse brain, Allen Brain Atlas, cellular resolution, in situ hybridization, brain region-specific gene expression, cell markers, brain organization
- MeSH terms
- Animals, Brain, Gene Expression Regulation, Hippocampus, Male, Mice, Inbred C57BL, Organ Specificity, RNA, Messenger, Genome, Computational Biology, Gene Expression Profiling, Genomics, Mice
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