Molecular and Functional Properties of Regional Astrocytes in the Adult Brain
Open accessAbstract
The molecular signature and functional properties of astroglial subtypes in the adult CNS remain largely undefined. By using translational ribosome affinity purification followed by RNA-Seq, we profiled astroglial ribosome-associated (presumably translating) mRNAs in major cortical and subcortical brain regions (cortex, hippocampus, caudate-putamen, nucleus accumbens, thalamus, and hypothalamus) of BAC aldh1l1-translational ribosome affinity purification (TRAP) mice (both sexes). We found that the expression of astroglial translating mRNAs closely follows the dorsoventral axis, especially from cortex/hippocampus to thalamus/hypothalamus posteriorly. This region-specific expression pattern of genes, such as synaptogenic modulator sparc and transcriptional factors (emx2, lhx2, and hopx), was validated by qRT-PCR and immunostaining in brain sections. Interestingly, cortical or subcortical astrocytes selectively promote neurite growth and synaptic activity of neurons only from the same region in mismatched cocultures, exhibiting region-matched astrocyte to neuron communication. Overall, these results generated new molecular signature of astrocyte types in the adult CNS, providing insights into their origin and functional diversity. SIGNIFICANCE STATEMENT We investigated the in vivo molecular and functional heterogeneity of astrocytes inter-regionally from adult brain. Our results showed that the expression pattern of ribosome-associated mRNA profiles in astrocytes closely follows the dorsoventral axis, especially posteriorly from cortex/hippocampus to thalamus/hypothalamus. In line with this, our functional results further demonstrated region-selective roles of cortical and subcortical astrocytes in regulating cortical or subcortical neuronal synaptogenesis and maturation. These in vivo studies provide a previously uncharacterized and important molecular atlas for exploring region-specific astroglial functions.
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Less is known about the transcriptomic heterogeneity of astrocytes across different cortical areas in the aging human brain.
“but less is known about the transcriptomic heterogeneity of astrocytes across different cortical areas in the aging human brain.”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [25]
The Introduction (page not provided) says earlier in vivo astrocyte gene profiling largely focused on the cortex or developing ages, and that regional human-brain datasets were not astrocyte-specific. This supports a general knowledge gap, but the paper studies adult mice and does not establish the claim specifically for different cortical areas in the aging human brain. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAstrocytes are organized into distinct functional-associated layers throughout the grey matter.
“Considering that astrocytes are organized into distinct functional‐associated layers throughout the GM [98, 99, 100, 101]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [99]
The Introduction describes spatial domains and region-dependent functional differences among astrocytes. But the Discussion says how astrocytes regulate local circuitry in different cortical layers remains essentially unknown; the paper does not establish distinct functional layers throughout grey matter. The indexed passages provide section labels but no page numbers. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRibo-tag restricts analysis to ribosome-associated mRNAs, which are more likely to be actively being made into proteins, providing a representation of the translational state of the cells.
“Ribo-tag restricts analysis to ribosome-associated mRNAs, which are more likely to be actively being made into proteins, providing a representation of the translational state of the cells, a similar approach to that used by others (Chai et al., 2017; Doyle et al., 2008; Morel et al., 2017).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Morel et al., 2017
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Cites
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 11,930 · 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
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
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,068 · see citing works
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313 · see citing works
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · see citing works
Azevedo, F. A. C., Carvalho, L. R. B., Grinberg, L. T., Farfel, J. M., Ferretti, R. E. L., Leite, R. E. P., Filho, W. J., Lent, R., & Herculano‐Houzel, S. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21974 · Cited by 2,337 · see citing works
Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis
Christopherson, K. S., Ullian, E. M., Stokes, C. C. A., Mullowney, C. E., Hell, J. W., Agah, A., Lawler, J., Mosher, D. F., Bornstein, P., & Barres, B. A. (2005) · Cell · doi:10.1016/j.cell.2004.12.020 · Cited by 1,688 · see citing works
Astrocyte Control of Synaptic Transmission and Neurovascular Coupling
Haydon, P. G., & Carmignoto, G. (2006) · Physiological Reviews · doi:10.1152/physrev.00049.2005 · Cited by 1,326 · see citing works
Application of a translational profiling approach for the comparative analysis of CNS cell types
Doyle, J. P., Dougherty, J. D., Heiman, M., Schmidt, E. F., Stevens, T. R., Ma, G., Bupp, S., Shrestha, P., Shah, R. D., Doughty, M. L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.029 · Cited by 912 · see citing works
Regulation of synaptic connectivity by glia.
Eroglu, C., & Barres, B. A. (2010) · Nature · doi:10.1038/nature09612 · Cited by 813 · see citing works
Chai, H., Diaz-Castro, B., Shigetomi, E., Monte, E., Octeau, J. C., Yu, X., Cohn, W., Rajendran, P. S., Vondriska, T. M., Whitelegge, J. P., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.029 · Cited by 769 · see citing works
Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors
Allen, N. J., Bennett, M. L., Foo, L. C., Wang, G. X., Chakraborty, C., Smith, S. J., & Barres, B. A. (2012) · Nature · doi:10.1038/nature11059 · Cited by 764 · see citing works
Genetic variability in the regulation of gene expression in ten regions of the human brain
UK Brain Expression Consortium, Ramasamy, A., North American Brain Expression Consortium, Trabzuni, D., Guelfi, S., Varghese, V., Smith, C., Walker, R., De, T., Coin, L., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3801 · Cited by 644 · see citing works
Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC
Kucukdereli, H., Allen, N. J., Lee, A. T., Feng, A., Ozlu, M. I., Conatser, L. M., Chakraborty, C., Workman, G., Weaver, M., Sage, E. H., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104977108 · Cited by 642 · see citing works
Heterogeneity of astrocytic form and function.
Oberheim, N. A., Goldman, S. A., & Nedergaard, M. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-61779-452-0_3 · Cited by 638 · see citing works
Astrocyte heterogeneity: an underappreciated topic in neurobiology
Zhang, Y., & Barres, B. A. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.06.005 · Cited by 548 · see citing works
Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair
Tsai, H., Li, H., Fuentealba, L. C., Molofsky, A. V., Taveira‐Marques, R., Zhuang, H., Tenney, A., Murnen, A. T., Fancy, S. P. J., Merkle, F. T., et al. (2012) · Science · doi:10.1126/science.1222381 · Cited by 529 · see citing works
Identification of diverse astrocyte populations and their malignant analogs
John Lin, C.-C., Yu, K., Hatcher, A., Huang, T.-W., Lee, H. K., Carlson, J., Weston, M. C., Chen, F., Zhang, Y., Zhu, W., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4493 · Cited by 525 · see citing works
Astrocyte Development and HeterogeneityPreprint
Bayraktar, O. A., Fuentealba, L. C., Álvarez-Buylla, A., & Rowitch, D. H. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020362 · Cited by 339 · see citing works
Hochstim, C., Deneen, B., Lukaszewicz, A., Zhou, Q., & Anderson, D. J. (2008) · Cell · doi:10.1016/j.cell.2008.02.046 · Cited by 331 · see citing works
Regan, M. R., Huang, Y. H., Kim, Y., Dykes‐Hoberg, M., Jin, L., Watkins, A. M., Bergles, D. E., & Rothstein, J. D. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0790-07.2007 · Cited by 314 · see citing works
Astrocyte-encoded positional cues maintain sensorimotor circuit integrity
Molofsky, A. V., Kelley, K. W., Tsai, H., Redmond, S., Chang, S., Madireddy, L., Chan, J. R., Baranzini, S. E., Ullian, E. M., & Rowitch, D. H. (2014) · Nature · doi:10.1038/nature13161 · Cited by 312 · see citing works
An anatomic gene expression atlas of the adult mouse brain
Ng, L., Bernard, A., Lau, C., Overly, C. C., Dong, H., Kuan, C. L., Pathak, D. S., Sunkin, S. M., Dang, C., Bohland, J. W., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2281 · Cited by 279 · see citing works
Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling
Farmer, W. T., Abrahamsson, T., Chierzi, S., Lui, C. G., Zaelzer, C. A., Jones, E. V., Bally, B. P., Chen, G. G., Théroux, J., Peng, J., et al. (2016) · Science · doi:10.1126/science.aab3103 · Cited by 270 · see citing works
Molecular comparison of GLT1 + and ALDH1L1 + astrocytes in vivo in astroglial reporter mice
Yang, Y., Vidensky, S., Jin, L., Jie, C., Lorenzini, I., Frankl, M., & Rothstein, J. D. (2010) · Glia · doi:10.1002/glia.21089 · Cited by 255 · see citing works
Self-citationNervenkitt: Notes on the history of the concept of neuroglia
Somjen, G. G. (1988) · Glia · doi:10.1002/glia.440010103 · Cited by 233 · see citing works
Molecular diversity of astrocytes with implications for neurological disorders
Bachoo, R. M., Kim, R. S., Ligon, K. L., Maher, E. A., Brennan, C. W., Billings, N., Chan, S., Li, C., Rowitch, D. H., Wong, W. H., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402140101 · Cited by 216 · see citing works
Morel, L., Higashimori, H., Tolman, M., & Yang, Y. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1167-14.2014 · Cited by 151 · see citing works
Self-citationYeh, T., Lee, D. Y., Gianino, S. M., & Gutmann, D. H. (2009) · Glia · doi:10.1002/glia.20845 · Cited by 119 · see citing works
Developmental Origins of Astrocyte Heterogeneity: The Final Frontier of CNS Development
Chaboub, L. S., & Deneen, B. (2012) · Developmental Neuroscience · doi:10.1159/000343723 · Cited by 111 · see citing works
Emx homeogenes and mouse brain development
Cecchi, C., & Boncinelli, E. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01608-8 · Cited by 88 · see citing works
Heterogeneity in gap junction expression in astrocytes cultured from different brain regions
Batter, D. K., Corpina, R. A., Roy, C., Spray, D. C., Hertzberg, E. L., & Kessler, J. A. (1992) · Glia · doi:10.1002/glia.440060309 · Cited by 85 · see citing works
Clasadonte, J., Morel, L., Barrios-Camacho, C. M., Chiang, M. S. R., Zhang, J., Iyer, L. K., Haydon, P. G., & Yang, Y. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.03.024 · Cited by 19 · see citing works
Self-citationBrain glutamate uptake: Regional distribution study from sensorimotor areas in the cat
Kerkerian, L., Nieoullon, A., & Dusticier, N. (1982) · Neurochemistry International · doi:10.1016/0197-0186(82)90064-x · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Kettenmann H (2015) Neuroglia, Ed 2. New York: Oxford UP.
Cited by
Sorted by citations
Normal aging induces A1-like astrocyte reactivity
Clarke, L. E., Liddelow, S. A., Chakraborty, C., Münch, A. E., Heiman, M., & Barres, B. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800165115 · Cited by 1,237 · see citing works
Identification of region-specific astrocyte subtypes at single cell resolution
Batiuk, M. Y., Martirosyan, A., Wahis, J., de Vin, F., Marneffe, C., Kusserow, C., Koeppen, J., Viana, J. F., Oliveira, J. F., Voet, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14198-8 · Cited by 805 · see citing works
The aging astrocyte transcriptome from multiple regions of the mouse brain.
Boisvert, M. M., Erikson, G. A., Shokhirev, M. N., & Allen, N. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.039 · Cited by 702 · see citing works
Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Endo, F., Kasai, A., Soto, J. S., Yu, X., Qu, Z., Hashimoto, H., Gradinaru, V., Kawaguchi, R., & Khakh, B. S. (2022) · Science · doi:10.1126/science.adc9020 · Cited by 560 · see citing works
Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis
Maniatis, S., Äijö, T., Vickovic, S., Braine, C., Kang, K., Mollbrink, A., Fagegaltier, D., Andrusivová, Ž., Saarenpää, S., Saiz-Castro, G., et al. (2019) · Science · doi:10.1126/science.aav9776 · Cited by 429 · see citing works
Beyond the GFAP-Astrocyte Protein Markers in the Brain
Jurga, A. M., Paleczna, M., Kadluczka, J., & Kuter, K. Z. (2021) · Biomolecules · doi:10.3390/biom11091361 · Cited by 319 · see citing works
Astrocyte Senescence and Alzheimer’s Disease: A Review
Han, X., Zhang, T., Liu, H., Mi, Y., & Gou, X. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00148 · Cited by 177 · see citing works
Shaping Synapses by the Neural Extracellular Matrix
Ferrer-Ferrer, M., & Dityatev, A. (2018) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2018.00040 · Cited by 169 · see citing works
Rizzardi, L. F., Hickey, P. F., Rodriguez DiBlasi, V., Tryggvadóttir, R., Callahan, C. M., Idrizi, A., Hansen, K. D., & Feinberg, A. P. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0297-8 · Cited by 146 · see citing works
Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease
Serrano-Pozo, A., Li, H., Li, Z., Muñoz-Castro, C., Jaisa-aad, M., Healey, M. A., Welikovitch, L. A., Jayakumar, R., Bryant, A. G., Noori, A., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01791-4 · Cited by 140 · see citing works
Regionally Distinct Astrocytes Display Unique Transcription Factor Profiles in the Adult Brain
Lozzi, B., Huang, T.-W., Sardar, D., Huang, A. Y.-S., & Deneen, B. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00061 · Cited by 78 · see citing works
Intracortical astrocyte subpopulations defined by astrocyte reporter Mice in the adult brain
Morel, L., Men, Y., Chiang, M. S. R., Tian, Y., Jin, S., Yelick, J., Higashimori, H., & Yang, Y. (2019) · Glia · doi:10.1002/glia.23545 · Cited by 59 · see citing works
Self-citationHenao‐Restrepo, J., López‐Murillo, C., Valderrama‐Carmona, P., Orozco‐Santa, N., Gomez, J., Gutiérrez‐Vargas, J., Moraga, R., Toledo, J., Littau, J. L., Härtel, S., et al. (2023) · Brain Pathology · doi:10.1111/bpa.13119 · Cited by 11 · see citing works
- Authors
- Morel, L., Chiang, M. S. R., Higashimori, H., Shoneye, T., Iyer, L. K., Yelick, J., Tai, A., & Yang, Y.
- Affiliations
- Tufts University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2017-08-07
- Volume
- 37
- Issue
- 36
- Pages
- 8706-8717
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC5588463
- OpenAlex
- W2744386347
- Cited by
- 243
- References
- 35
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 31 · 2023: 24 · 2022: 28 · 2021: 32 · 2020: 39 · 2019: 23 · 2018: 27 · 2017: 2
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Center for Neuroscience Research
- National Institute of Mental Health (R01MH099554, R01MH106490)
- National Institute of General Medical Sciences (R25GM066567)
- National Institute of Neurological Disorders and Stroke (R03NS079805, R21NS087391, P30NS047243)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- astrocytes, regional heterogeneity, dorsal-ventral axis, ribosome-associated mRNA, astrocyte-neuron communication, synaptogenesis, neuronal maturation, SPARC, Emx2, Lhx2, HOPX, hippocampus, thalamus, hypothalamus, caudate-putamen, nucleus accumbens, adult brain
- MeSH terms
- Animals, Astrocytes, Brain, Female, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Transcription Factors, Gene Expression Profiling, Mice
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