气候变化领域集成服务门户(CCPortal): Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment

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DOI	10.1126/science.aax2537
	Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment
	Trujillo C.A.; Rice E.S.; Schaefer N.K.; Chaim I.A.; Wheeler E.C.; Madrigal A.A.; Buchanan J.; Preissl S.; Wang A.; Negraes P.D.; Szeto R.A.; Herai R.H.; Huseynov A.; Ferraz M.S.A.; Borges F.S.; Kihara A.H.; Byrne A.; Marin M.; Vollmers C.; Brooks A.N.; Lautz J.D.; Semendeferi K.; Shapiro B.; Yeo G.W.; Smith S.E.P.; Green R.E.; Muotri A.R.
发表日期	2021
ISSN	0036-8075
卷号	371 期号:6530
英文摘要	The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of NOVA1. Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
英文关键词	amino acid; CRISPR associated endonuclease Cas9; n methyl dextro aspartic acid receptor; NOVA1 protein; protein; transcriptome; unclassified drug; nerve protein; NOVA1 protein, human; RNA binding protein; allele; amino acid; antigen; divergence; gene expression; genome; Neanderthal; nervous system; protein; allele; alternative RNA splicing; Article; cell proliferation; fossil hominin; gene editing; gene expression; genetic difference; genetic variation; haplotype; Homo denisovan; Homo neanderthalensis; human; human genome; immunoprecipitation; induced pluripotent stem cell; mental disease; nerve cell; nerve cell differentiation; organoid; phenotype; RNA sequence; single nucleotide polymorphism; synaptogenesis; amino acid substitution; animal; binding site; brain cortex; CRISPR Cas system; cytology; evolution; gene expression regulation; genetics; genome; growth, development and aging; hominid; metabolism; nerve cell network; physiology; synapse; Alleles; Alternative Splicing; Amino Acid Substitution; Animals; Binding Sites; Biological Evolution; Cell Proliferation; Cerebral Cortex; CRISPR-Cas Systems; Gene Expression Regulation, Developmental; Genetic Variation; Genome; Genome, Human; Haplotypes; Hominidae; Humans; Induced Pluripotent Stem Cells; Neanderthals; Nerve Net; Nerve Tissue Proteins; Neurons; Organoids; RNA-Binding Proteins; Synapses
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/245782
作者单位	Department of Pediatrics, Department of Cellular and Molecular Medicine, School of Medicine, Center for Academic Research and Training in Anthropogeny (CARTA), Kavli Institute for Brain and Mind, University of California, San Diego, San Diego, CA 92037, United States; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, United States; Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, San Diego, CA 92093, United States; Department of Cellular and Molecular Medicine, Center for Epigenomics, University of California, San Diego, San Diego, CA 92093, United States; Experimental Multiuser Laboratory (LEM), Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR, 80215-901, Brazil; National Heart and Lung Institute, Imperial College London, London, SW3 6LY, United Kingdom; Laboratório de Neurogenética, Centro de Matemática, Computação e Cognição, Unive...
推荐引用方式 GB/T 7714	Trujillo C.A.,Rice E.S.,Schaefer N.K.,et al. Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment[J],2021,371(6530).
APA	Trujillo C.A..,Rice E.S..,Schaefer N.K..,Chaim I.A..,Wheeler E.C..,...&Muotri A.R..(2021).Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment.Science,371(6530).
MLA	Trujillo C.A.,et al."Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment".Science 371.6530(2021).