Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice
Open accessAbstract
Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.
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hiPSC glial mouse chimeric brains offer the possibility to study human astrocytes from patients in contexts amenable to in vivo experimentation.
“hiPSC glial mouse chimeric brains, in which hiPSC differentiate into human astrocytes, oligodendrocytes, and their progenitors, offer the possibility to study human astrocytes from patients in contexts amenable to in vivo experimentation113,114”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [113]
The Discussion describes human glial-chimeric mice as a model for studying human glial cells, including pathological aspects of their biology, in the live adult brain. However, the Experimental Procedures say the transplanted progenitors came from fetal tissue, not patient-derived hiPSCs. The Results also report no detectable human oligodendroglia in these mice, so the cited paper does not support that detail of the citing sentence. (LLM, conf=0.88)
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References 40 · Cited by 635
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- Authors
- Han, X., Chen, M., Wang, F., Windrem, M., Wang, S., Shanz, S., Xu, Q., Oberheim, N. A., Bekar, L., Betstadt, S., Silva, A. J., Takano, T., Goldman, S. A., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- University of California, Los Angeles (US)
- Corresponding author
- Goldman, Steven A.
- Nedergaard, Maiken
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 12
- Issue
- 3
- Pages
- 342-353
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3700554
- OpenAlex
- W2115565454
- Cited by
- 635
- References
- 40
- Citations by year
- 2026: 26 · 2025: 31 · 2024: 39 · 2023: 42 · 2022: 46 · 2021: 68 · 2020: 47 · 2019: 54 · 2018: 45 · 2017: 61 · 2016: 48 · 2015: 48 · 2014: 46 · 2013: 32
- FWCI
- 28.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH113071)
- National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS078167, R01NS075177, R01NS075345, R01NS052534, R01NS106969)
- 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
- astrocytes, chimeric mice, synaptic plasticity, long-term potentiation, learning, electrical coupling, calcium signaling, human evolution, fear conditioning, object location memory
- MeSH terms
- Animals, Astrocytes, Brain, Calcium, Cell Differentiation, Hippocampus, Humans, Learning, Neuroglia, Neuronal Plasticity, Stem Cells, Synapses, Prosencephalon, Mice
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