scholarly journals CHD8 safeguards early neuroectoderm differentiation in human ESCs and protects from apoptosis during neurogenesis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Song Ding ◽  
Xianchun Lan ◽  
Yajing Meng ◽  
Chenchao Yan ◽  
Mao Li ◽  
...  
Keyword(s):  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Directed Differentiation ◽  
Loss Of Function ◽  
Human Escs ◽  
Chromatin Remodelers ◽  
Spectrum Disorders ◽  
Pluripotency Maintenance

AbstractThe chromatin remodeler CHD8, which belongs to the ATP-dependent chromatin remodelers CHD family, is one of the most high-risk mutated genes in autism spectrum disorders. However, the role of CHD8 in neural differentiation and the mechanism of CHD8 in autism remains unclear, despite there are a few studies based on the CHD8 haploinsufficient models. Here, we generate the CHD8 knockout human ESCs by CRISPR/Cas9 technology and characterize the effect of loss-of-function of CHD8 on pluripotency maintenance and lineage determination by utilizing efficient directed differentiation protocols. The results show loss-of-function of CHD8 does not affect human ESC maintenance although having slight effect on proliferation and cell cycle. Interestingly, CHD8 depletion results in defective neuroectoderm differentiation, along with severe cell death in neural progenitor stage. Transcriptome analysis also indicates CHD8 does not alter the expression of pluripotent genes in ESC stage, but in neural progenitor cells depletion of CHD8 induces the abnormal expression of the apoptosis genes and suppresses neuroectoderm-related genes. These results provide the evidence that CHD8 plays an essential role in the pluripotency exit and neuroectoderm differentiation as well as the regulation of apoptosis during neurogenesis.

scholarly journals Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 470
Author(s):  
Jeremy W. Prokop ◽  
Caleb P. Bupp ◽  
Austin Frisch ◽  
Stephanie M. Bilinovich ◽  
Daniel B. Campbell ◽  
...  
Keyword(s):  
Brain Development ◽  
Neural Progenitor Cells ◽  
Neurodevelopmental Disorder ◽  
Fetal Brain ◽  
Missense Variant ◽  
Neural Progenitor ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Systematic Analysis ◽  
Function Expression

Ornithine decarboxylase 1 (ODC1 gene) has been linked through gain-of-function variants to a rare disease featuring developmental delay, alopecia, macrocephaly, and structural brain anomalies. ODC1 has been linked to additional diseases like cancer, with growing evidence for neurological contributions to schizophrenia, mood disorders, anxiety, epilepsy, learning, and suicidal behavior. The evidence of ODC1 connection to neural disorders highlights the need for a systematic analysis of ODC1 genotype-to-phenotype associations. An analysis of variants from ClinVar, Geno2MP, TOPMed, gnomAD, and COSMIC revealed an intellectual disability and seizure connected loss-of-function variant, ODC G84R (rs138359527, NC_000002.12:g.10444500C > T). The missense variant is found in ~1% of South Asian individuals and results in 2.5-fold decrease in enzyme function. Expression quantitative trait loci (eQTLs) reveal multiple functionally annotated, non-coding variants regulating ODC1 that associate with psychiatric/neurological phenotypes. Further dissection of RNA-Seq during fetal brain development and within cerebral organoids showed an association of ODC1 expression with cell proliferation of neural progenitor cells, suggesting gain-of-function variants with neural over-proliferation and loss-of-function variants with neural depletion. The linkage from the expression data of ODC1 in early neural progenitor proliferation to phenotypes of neurodevelopmental delay and to the connection of polyamine metabolites in brain function establish ODC1 as a bona fide neurodevelopmental disorder gene.

Critical role of dysfunctional mitochondria and defective mitophagy in autism spectrum disorders

2021 ◽  
Vol 168 ◽  
pp. 138-145
Author(s):  
Yuan-Mei Wang ◽  
Ming-Yue Qiu ◽  
Qing Liu ◽  
Huang Tang ◽  
Hong-Feng Gu
Keyword(s):  
Autism Spectrum Disorders ◽  
Critical Role ◽  
Autism Spectrum ◽  
Spectrum Disorders

A Role of CPEB1 in the Modulation of Proliferation and Neuronal Maturation of Rat Primary Neural Progenitor Cells

2013 ◽  
Vol 38 (9) ◽  
pp. 1960-1972 ◽  
Author(s):  
Ki Chan Kim ◽  
Ji-Woon Kim ◽  
Chang Soon Choi ◽  
Sun Young Han ◽  
Jae Hoon Cheong ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Neuronal Maturation

scholarly journals Mutation analysis of the NRXN1 gene in autism spectrum disorders

2016 ◽  
Vol 19 (2) ◽  
pp. 17-22 ◽  
Author(s):  
H Onay ◽  
D Kacamak ◽  
AN Kavasoglu ◽  
B Akgun ◽  
M Yalcinli ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum Disorders ◽  
Children And Adolescents ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Syndromic Autism ◽  
Spectrum Disorders ◽  
Strong Candidate ◽  
Reduced Penetrance

AbstractThe aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient. The S14L and L748I mutations have been described in the patients with autism before. Both of these mutations were inherited from their father. In this study, two of 30 (6.7%) autism spectrum disorder (ASD) patients carrying NRXN1 gene mutations were detected. It indicates that variants in the NRXN1 gene might confer a risk of developing nonsyndromic ASD. However, due to the reduced penetrance in the gene, the causal role of the NRXN1 gene mutations must be evaluated carefully in all cases.

scholarly journals Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse

2018 ◽  
Vol 115 (12) ◽  
pp. E2725-E2733 ◽  
Author(s):  
Yulong Cai ◽  
Xiaotong Tang ◽  
Xi Chen ◽  
Xin Li ◽  
Ying Wang ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Liver X Receptor ◽  
Self Renewal ◽  
Spectrum Disorders ◽  
Deficient Mice

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor β (LXRβ) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRβ in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRβ-null mice. In addition, LXRβ deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRβ in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRβ-deficient mice.

scholarly journals The role of genetic factors and pre- and peri-natal influences in the etiology of autism spectrum disorders – indications for genetic referral

2016 ◽  
Vol 50 (3) ◽  
pp. 543-554 ◽  
Author(s):  
Filip Rybakowski ◽  
Izabela Chojnicka ◽  
Piotr Dziechciarz ◽  
Andrea Horvath ◽  
Małgorzata Janas-Kozik ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Genetic Factors ◽  
Autism Spectrum ◽  
Spectrum Disorders

scholarly journals Preparation for Independent Life of People with ASD and Other Developmental Disorders in The Autonomous Noncommercial Organization «Adain Lo» (ANO «Adain Lo»).

2018 ◽  
Vol 16 (1) ◽  
pp. 29-35
Author(s):  
A.A. Ginsburg ◽  
M.E. Gitshabash ◽  
Ya.L. Ivanova
Keyword(s):  
Developmental Disorders ◽  
Autism Spectrum ◽  
Adults With Autism ◽  
Saint Petersburg ◽  
Independent Life ◽  
Spectrum Disorders ◽  
Self Service ◽  
Role Of Parents ◽  
Commercial Organization

The problems of preparation of children and adults with autism spectrum disorders and other developmental disabilities for independent life, modern ways of development of their independence are considered. The role of parents in this process and parent-specialist interaction are stressed. The techniques of tutor support, parents and other specialists are described. Presented techniques are realized in autonomous non-commercial organization «Adain Lo» (Saint-Petersburg) and aimed for maintenance of independent life, self-service, game, communication and education of people with special needs.

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