Modeling human-specific interlaminar astrocytes in the mouse cerebral cortex.
Open accessAbstract
Astrocytes, a highly heterogeneous population of glial cells, serve as essential regulators of brain development and homeostasis. The heterogeneity of astrocyte populations underlies the diversity in their functions. In addition to the typical mammalian astrocyte architecture, the cerebral cortex of humans exhibits a radial distribution of interlaminar astrocytes in the supragranular layers. These primate‐specific interlaminar astrocytes are located in the superficial layer and project long processes traversing multiple layers of the cerebral cortex. However, due to the lack of accessible experimental models, their functional properties and their role in regulating neuronal circuits remain unclear. Here we modeled human interlaminar astrocytes in humanized glial chimeric mice by engrafting astrocytes differentiated from human‐induced pluripotent stem cells into the mouse cortex. This model provides a novel platform for understanding neuron‐glial interaction and its alterations in neurological diseases.
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Engraftment of human-specific ILAs in the first layer of the mouse cortex allows the study of cells that retain intrinsic properties of human ILAs (such as process length and tortuosity, the presence of club-ending and typical interlaminar markers) and integrate into the host environment, contacting synapses, capillaries, and the pia.
“Engraftment of human-specific ILAs in the first layer of the mouse cortex (Padmashri et al., 2021), also known as the creation of chimeric mice. This innovative technique allows the study of cells that retain the intrinsic properties of human ILAs (such as process length and tortuosity, the presence of club-ending and typical interlaminar markers) and integrate into the host environment, contact”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Padmashri et al., 2021
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Experimental — accuracy not yet measuredILA processes contact VGLUT1+ synapses in a chimeric model with human astrocytes transplanted into mice.
“and VGLUT1+ synapses in a chimeric model with human astrocytes transplanted into mice (Padmashri et al., 2021).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Padmashri et al., 2021
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Conserved cell types with divergent features in human versus mouse cortex
Hodge, R. D., Bakken, T. E., Miller, J. A., Smith, K. A., Barkan, E. R., Graybuck, L. T., Close, J. L., Long, B., Johansen, N., Penn, O., et al. (2019) · Nature · doi:10.1038/s41586-019-1506-7 · Cited by 1,775 · cited 2× · see citing works
“most results were derived from rodent astrocytes, which have interspecies differences with human astrocytes (Hodge et al., 2019; Oberheim et al., 2009; Zhang et al., 2016) and the structural and functional proper-”
BackgroundPSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease
Oksanen, M., Petersen, A. J., Naumenko, N., Puttonen, K., Lehtonen, Š., Gubert Olivé, M., Shakirzyanova, A., Leskelä, S., Sarajärvi, T., Viitanen, M., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.016 · Cited by 332 · see citing works
Chen, C., Jiang, P., Xue, H., Peterson, S. E., Tran, H. T., McCann, A. E., Parast, M. M., Li, S., Pleasure, D. E., Laurent, L. C., et al. (2014) · Nature Communications · doi:10.1038/ncomms5430 · Cited by 219 · see citing works
Coiro, P., Padmashri, R., Suresh, A., Spartz, E., Pendyala, G., Chou, S., Jung, Y., Meays, B., Roy, S., Gautam, N., et al. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.022 · Cited by 105 · see citing works
Flagged first, then by citations
Research works printed but not linked: 34
- Araque, A., Li, N., Doyle, R. T., & Haydon, P. G. (2000). SNARE protein‐dependent glutamate release from astrocytes. The Journal of Neuroscience, 202, 666– 673. PMC6772413 10632596
- Baldwin, K. T., & Eroglu, C. (2017). Molecular mechanisms of astrocyte‐induced synaptogenesis. Current Opinion in Neurobiology, 45, 113– 120. 28570864 PMC5573249
- Bayer, S. A., & Altman, J. (1991). Neocortical development. New York, NY: Raven Press.
- Bazargani, N., & Attwell, D. (2016). Astrocyte calcium signaling: The third wave. Nature Neuroscience, 192, 182– 189. 26814587
- Buldyrev, S. V., Cruz, L., Gomez‐Isla, T., Gomez‐Tortosa, E., Havlin, S., Le, R., … Hyman, B. T. (2000). Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias. Proceedings of the National Academy of Sciences of the United States of America, 9710, 5039– 5043. PMC25777 10805766
- Canals, I., Ginisty, A., Quist, E., Timmerman, R., Fritze, J., Miskinyte, G., … Ahlenius, H. (2018). Rapid and efficient induction of functional astrocytes from human pluripotent stem cells. Nature Methods, 159, 693– 696. 30127505
- Colombo, J. A., Gayol, S., Yanez, A., & Marco, P. (1997). Immunocytochemical and electron microscope observations on astroglial interlaminar processes in the primate neocortex. Journal of Neuroscience Research, 484, 352– 357. 9169861
- Colombo, J. A., Lipina, S., Yanez, A., & Puissant, V. (1997). Postnatal development of interlaminar astroglial processes in the cerebral cortex of primates. International Journal of Developmental Neuroscience, 157, 823– 833. 9580494
- Colombo, J. A., Quinn, B., & Puissant, V. (2002). Disruption of astroglial interlaminar processes in Alzheimer's disease. Brain Research Bulletin, 582, 235– 242. 12127023
- Colombo, J. A., & Reisin, H. D. (2004). Interlaminar astroglia of the cerebral cortex: A marker of the primate brain. Brain Research, 10061, 126– 131. 15047031
- Colombo, J. A., Reisin, H. D., Jones, M., & Bentham, C. (2005). Development of interlaminar astroglial processes in the cerebral cortex of control and Down's syndrome human cases. Experimental Neurology, 1931, 207– 217. 15817279
- Falcone, C., Wolf‐Ochoa, M., Amina, S., Hong, T., Vakilzadeh, G., Hopkins, W. D., … Martinez‐Cerdeno, V. (2019). Cortical interlaminar astrocytes across the therian mammal radiation. The Journal of Comparative Neurology, 52710, 1654– 1674. PMC6465161 30552685
- Forscher, P., & Smith, S. J. (1988). Actions of cytochalasins on the organization of Actin filaments and microtubules in a neuronal growth cone. The Journal of Cell Biology, 107, 1505– 1516. 3170637 PMC2115246
- Han, X., Chen, M., Wang, F., Windrem, M., Wang, S., Shanz, S., … Nedergaard, M. (2013). Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell, 123, 342– 353. PMC3700554 23472873
- Hirabayashi, Y., & Gotoh, Y. (2005). Stage‐dependent fate determination of neural precursor cells in mouse forebrain. Neuroscience Research, 514, 331– 336. 15740796
- Jones, V. C., Atkinson‐Dell, R., Verkhratsky, A., & Mohamet, L. (2017). Aberrant iPSC‐derived human astrocytes in Alzheimer's disease. Cell Death & Disease, 83, e2696. PMC5386580 28333144
- Khakh, B. S., & Deneen, B. (2019). The emerging nature of astrocyte diversity. Annual Review of Neuroscience, 42, 187– 207. 31283899
- Khakh, B. S., & Sofroniew, M. V. (2015). Diversity of astrocyte functions and phenotypes in neural circuits. Nature Neuroscience, 187, 942– 952. PMC5258184 26108722
- Krencik, R., van Asperen, J. V., & Ullian, E. M. (2017). Human astrocytes are distinct contributors to the complexity of synaptic function. Brain Research Bulletin, 129, 66– 73. 27570101 PMC5323268
- Miller, F. D., & Gauthier, A. S. (2007). Timing is everything: Making neurons versus glia in the developing cortex. Neuron, 543, 357– 369. 17481390
- Mountcastle, V. B. (1997). The columnar organization of the neocortex. Brain, 120 (Pt 4, 701– 722. 9153131
- Oberheim, N. A., Goldman, S. A., & Nedergaard, M. (2012). Heterogeneity of astrocytic form and function. Methods in Molecular Biology, 814, 23– 45. 22144298 PMC3506190
- Oberheim, N. A., Takano, T., Han, X., He, W., Lin, J. H., Wang, F., … Nedergaard, M. (2009). Uniquely hominid features of adult human astrocytes. The Journal of Neuroscience, 2910, 3276– 3287. PMC2819812 19279265
- Oberheim, N. A., Wang, X., Goldman, S., & Nedergaard, M. (2006). Astrocytic complexity distinguishes the human brain. Trends in Neurosciences, 2910, 547– 553. 16938356
- Olsen, M. L., Khakh, B. S., Skatchkov, S. N., Zhou, M., Lee, C. J., & Rouach, N. (2015). New insights on astrocyte ion channels: Critical for homeostasis and neuron‐glia signaling. The Journal of Neuroscience, 3541, 13827– 13835. PMC4604221 26468182
- Reisin, H. D., & Colombo, J. A. (2004). Glial changes in primate cerebral cortex following long‐term sensory deprivation. Brain Research, 10001‐2, 179– 182. 15053965
- Russo, F. B., Freitas, B. C., Pignatari, G. C., Fernandes, I. R., Sebat, J., Muotri, A. R., & Beltrao‐Braga, P. C. B. (2017). Modeling the interplay between neurons and astrocytes in autism using human induced pluripotent stem cells. Biological Psychiatry. 83(7), 569–578. doi:10.1016/j.biopsych.2017.09.021 29129319 · DOI
- Sofroniew, M. V., & Vinters, H. V. (2010). Astrocytes: Biology and pathology. Acta Neuropathologica, 1191, 7– 35. PMC2799634 20012068
- Taupin, P., & Gage, F. H. (2002). Adult neurogenesis and neural stem cells of the central nervous system in mammals. Journal of Neuroscience Research, 696, 745– 749. 12205667
- Vainchtein, I. D., Chin, G., Cho, F. S., Kelley, K. W., Miller, J. G., Chien, E. C., … Molofsky, A. V. (2018). Astrocyte‐derived interleukin‐33 promotes microglial synapse engulfment and neural circuit development. Science, 359, 1269– 1273. 29420261 PMC6070131
- Van Horn, M. R., & Ruthazer, E. S. (2018). Glial regulation of synapse maturation and stabilization in the developing nervous system. Current Opinion in Neurobiology, 54, 113– 119. 30347385
- Verkhratsky, A., & Nedergaard, M. (2018). Physiology of Astroglia. Physiological Reviews, 981, 239– 389. PMC6050349 29351512
- Windrem, M. S., Osipovitch, M., Liu, Z., Bates, J., Chandler‐Militello, D., Zou, L., … Goldman, S. A. (2017). Human iPSC glial mouse chimeras reveal glial Contributions to schizophrenia. Cell Stem Cell, 21, 195– 208.e6. 28736215 PMC5576346
- Zhang, Y., Sloan, S. A., Clarke, L. E., Caneda, C., Plaza, C. A., Blumenthal, P. D., … Barres, B. A. (2016). Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron, 891, 37– 53. PMC4707064 26687838
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Wallace, J. L., & Pollen, A. A. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00760-3 · Cited by 82 · see citing works
Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain
Ciani, C., & Falcone, C. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1477753 · Cited by 11 · see citing works
Varicose projection astrocytes: Conserved reactive cells in brain pathology
Ciani, C., Pistorio, G., Giancola, S., Mearelli, M., Mongelli, F. E., Forouzeh, D., Campos Soares, L., Gonzalez Martin, M., Lichtenstein, M. E., Mio, L., et al. (2026) · Science Advances · doi:10.1126/sciadv.ady8204 · Cited by 4 · see citing works
- Authors
- Padmashri, R., Ren, B., Oldham, B., Jung, Y., Gough, R., & Dunaevsky, A.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Dunaevsky, Anna
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2020-07-29
- Volume
- 529
- Issue
- 4
- Pages
- 802-810
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- PMC
- PMC7818222
- OpenAlex
- W3042019624
- Cited by
- 21
- References
- 4
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Comparative Neurology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS109381)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cerebral cortex, supragranular layers, neuron-glia interactions, astrocyte heterogeneity, neurological disorders
- MeSH terms
- Adolescent, Animals, Astrocytes, Cells, Cultured, Cerebral Cortex, Female, Humans, Male, Mice, Transgenic, Mice, Induced Pluripotent Stem Cells, Mice, 129 Strain
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