ArticleScience translational medicine2015
Dysregulation of astrocyte extracellular signaling in Costello syndrome.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 95 citations in OpenAlex.
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- Developmental arrest of astrocyte lineage in Snai2 deletion mice: implication for the intellectual disability in patients with Waardenburg syndrome.Translational psychiatry · 2025Article
- Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models.The Journal of clinical investigation · 2025Article
- mTOR activation induces endolysosomal remodeling and nonclassical secretion of IL-32 via exosomes in inflammatory reactive astrocytes.Journal of neuroinflammation · 2024Article
- Astrocyte Regulation of Synapse Formation, Maturation, and Elimination.Cold Spring Harbor perspectives in biology · 2024Review
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
- RAS pathway: The new frontier of brain mosaicism in epilepsy.Neurobiology of disease · 2023Review
- Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology.Stem cell reports · 2023Article
- Chemogenetic manipulation of astrocyte activity at the synapse- a gateway to manage brain disease.Frontiers in cell and developmental biology · 2023Review
- Asteroid impact: the potential of astrocytes to modulate human neural networks within organoids.Frontiers in neuroscience · 2023Review
- Zika virus alters centrosome organization to suppress the innate immune response.EMBO reports · 2022Article
- Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders.Nature neuroscience · 2022Article
- Tropism of SARS-CoV-2 for human cortical astrocytes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Human Astrocytes Exhibit Tumor Microenvironment-, Age-, and Sex-Related Transcriptomic Signatures.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Assessing Gq-GPCR-induced human astrocyte reactivity using bioengineered neural organoids.The Journal of cell biology · 2022Article
- Review
- Opportunities and challenges of glioma organoids.Cell communication and signaling : CCS · 2021Review
- Dysregulated ECM remodeling proteins lead to aberrant osteogenesis of Costello syndrome iPSCs.Stem cell reports · 2021Article
- Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
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9 authors at 2 institutions in 1 country.
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Abstract
Astrocytes produce an assortment of signals that promote neuronal maturation according to a precise developmental timeline. Is this orchestrated timing and signaling altered in human neurodevelopmental disorders? To address this question, the astroglial lineage was investigated in two model systems of a developmental disorder with intellectual disability caused by mutant Harvey rat sarcoma viral oncogene homolog (HRAS) termed Costello syndrome: mutant HRAS human induced pluripotent stem cells (iPSCs) and transgenic mice. Human iPSCs derived from patients with Costello syndrome differentiated to astroglia more rapidly in vitro than those derived from wild-type cell lines with normal HRAS, exhibited hyperplasia, and also generated an abundance of extracellular matrix remodeling factors and proteoglycans. Acute treatment with a farnesyl transferase inhibitor and knockdown of the transcription factor SNAI2 reduced expression of several proteoglycans in Costello syndrome iPSC-derived astrocytes. Similarly, mice in which mutant HRAS was expressed selectively in astrocytes exhibited experience-independent increased accumulation of perineuronal net proteoglycans in cortex, as well as increased parvalbumin expression in interneurons, when compared to wild-type mice. Our data indicate that astrocytes expressing mutant HRAS dysregulate cortical maturation during development as shown by abnormal extracellular matrix remodeling and implicate excessive astrocyte-to-neuron signaling as a possible drug target for treating mental impairment and enhancing neuroplasticity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.