Science (American Association for the Advancement of Science), 2022-01, Vol.375 (6579), p.eabf5546-eabf5546
2022
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- Autor(en) / Beteiligte
- Titel
- Amplification of human interneuron progenitors promotes brain tumors and neurological defects
- Ist Teil von
- Science (American Association for the Advancement of Science), 2022-01, Vol.375 (6579), p.eabf5546-eabf5546
- Ort / Verlag
- United States: The American Association for the Advancement of Science
- Erscheinungsjahr
- 2022
- Quelle
- Science Online_科学在线
- Beschreibungen/Notizen
- Evolutionary development of the human brain is characterized by the expansion of various brain regions. Here, we show that developmental processes specific to humans are responsible for malformations of cortical development (MCDs), which result in developmental delay and epilepsy in children. We generated a human cerebral organoid model for tuberous sclerosis complex (TSC) and identified a specific neural stem cell type, caudal late interneuron progenitor (CLIP) cells. In TSC, CLIP cells over-proliferate, generating excessive interneurons, brain tumors, and cortical malformations. Epidermal growth factor receptor inhibition reduces tumor burden, identifying potential treatment options for TSC and related disorders. The identification of CLIP cells reveals the extended interneuron generation in the human brain as a vulnerability for disease. In addition, this work demonstrates that analyzing MCDs can reveal fundamental insights into human-specific aspects of brain development.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075, 1095-9203eISSN: 1095-9203DOI: 10.1126/science.abf5546Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7613689
- Format
- –
- Schlagworte
- Abnormalities, Alleles, Animal models, Autism, Brain, Brain - embryology, Brain - pathology, Brain cancer, Brain Neoplasms - drug therapy, Brain Neoplasms - genetics, Brain Neoplasms - metabolism, Brain Neoplasms - pathology, Brain tumors, Carcinogenesis, Cell Lineage, Cell Proliferation, Cells (biology), Chromosomes, Complexity, Context, Defects, Disabilities, Disease Progression, Disorders, Epidermal growth factor, Epidermal growth factor receptors, Epilepsy, ErbB Receptors - antagonists & inhibitors, ErbB Receptors - metabolism, Fetuses, Gene Expression Profiling, Gene sequencing, Genetic analysis, Genetic disorders, Genetics, Growth factors, Heterozygosity, Homology, Humans, Induced Pluripotent Stem Cells, Interneurons - cytology, Interneurons - physiology, Lesions, Loss of Heterozygosity, Mental disorders, Mutation, Neural Stem Cells - cytology, Neural Stem Cells - physiology, Neurodevelopmental disorders, Organoids, Phenotypes, Pregnancy, Progenitor cells, Rapamycin, RNA-Seq, Signaling, Signs and symptoms, Stem cells, Tissue analysis, TOR protein, TOR Serine-Threonine Kinases - metabolism, Tuberous sclerosis, Tuberous Sclerosis - drug therapy, Tuberous Sclerosis - genetics, Tuberous Sclerosis - metabolism, Tuberous Sclerosis - pathology, Tuberous Sclerosis Complex 1 Protein - genetics, Tuberous Sclerosis Complex 1 Protein - metabolism, Tuberous Sclerosis Complex 2 Protein - genetics, Tuberous Sclerosis Complex 2 Protein - metabolism, Tumorigenesis, Tumors