Integrating Molecular and Organismal Analyses of Rai1, The Causal Gene for Smith-Magenis Syndrome
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ABSTRACT:
PROVIDER: PRJNA320885 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3480140_1.fastq.gz | Fastqsanger.gz | |||
| SRR3480140_2.fastq.gz | Fastqsanger.gz | |||
| SRR3480220_1.fastq.gz | Fastqsanger.gz | |||
| SRR3480220_2.fastq.gz | Fastqsanger.gz | |||
| SRR3480141_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE337750 | GEO
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE337485 | GEO
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE337359 | GEO
Project description:Human brain development proceeds on an unusually long timeline, fostering the species' cognitive advantages. Retinoic Acid Induced 1 (RAI1) gene encodes a nucleosome-binding protein haploinsufficient in Smith–Magenis Syndrome (SMS), a neurodevelopmental disorder characterized by cognitive deficits with autistic features. However, the role of RAI1 in human neurodevelopment remains unexplored experimentally. Here, we generated isogenic heterozygous and homozygous RAI1 loss-of-function human embryonic stem cell lines and interrogated the roles of RAI1 in neurodevelopmental gene regulation. A longitudinal transcriptome study during in vitro cortical development revealed that RAI1 deficiency accelerates developmental transcriptome progression, as indicated by the induction of synaptic genes. Single-cell RNA-seq analysis revealed that RAI1-deficient neuroprogenitors acquire a transient mesoderm-like gene expression signature followed by pro-neuronal maturation gene expression in postmitotic neurons. Unexpectedly, the developmental acceleration signature was exacerbated during NGN2-induced excitatory neuron differentiation, suggesting functional interplay between RAI1 and NGN2-driven programs. Together, these results identify RAI1 as a suppressor of the mesodermal lineage program and as a novel brake that slows the tempo of human neurodevelopmental gene expression.
2026-07-08 | GSE336167 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-01-03 | GSE81207 | GEO
Project description:Smith-Magenis syndrome (SMS) is a developmental disability/multiple congenital anomaly disorder resulting from haploinsufficiency of RAI1. It is characterized by distinctive facial features, brachydactyly, sleep disturbances and stereotypic behaviors. We investigated a cohort of 15 individuals with a clinical suspicion of SMS, who showed neither deletion in the SMS critical region nor damaging variants in RAI1. Potentially deleterious variants were identified in nine of these subjects using whole-exome sequencing. Eight of these changes affect KMT2D, ZEB2, MAP2K2, GLDC, CASK, MECP2, KDM5C and POGZ, known to be associated with Kabuki syndrome 1, Mowat-Wilson syndrome, cardiofaciocutaneous syndrome, glycine encephalopathy, mental retardation and microcephaly with pontine and cerebellar hypoplasia, X-linked mental retardation 13, X-linked mental retardation Claes-Jensen type and White-Sutton syndrome, respectively. The ninth individual carries a de novo variant in JAKMIP1, a regulator of neuronal translation that was recently found deleted in a patient with autism spectrum disorder. Analyses of coexpression and biomedical text mining suggest that these pathologies and SMS are part of the same disease network. Further support for this hypothesis was obtained from transcriptome profiling that showed that the expression levels of both Zeb2 and Map2k2 are perturbed in Rai1-/- mice. As an orthogonal approach to potentially contributory disease gene variants, we used chromatin conformation capture to reveal chromatin contacts between RAI1 and the loci flanking ZEB2 and GLDC, as well as between RAI1 and human orthologs of the genes that show perturbed expression in our Rai1-/- mouse model. These holistic studies of RAI1 and its interactions allow insights into SMS and other disorders associated with intellectual disability and behavioral abnormalities. Our findings support a pan-genomic approach to the molecular diagnosis of a distinctive disorder.
2017-02-12 | GSE83420 | GEO
Project description: Not available
| S-EPMC5098476 | biostudies-literature
Project description:The goals of this study are to harvest adult-onset Rai1-deficient mouse brains from hypothalamus and compare the transcriptome with their wild-type littermates. Methods: mRNA profiles from Rai1 conditional knockouts and wild-type mice were generated by deep sequencing, in duplicate using Illumina system. Conclusions: Our study suggests that Rai1 preferentially regulate genes involved in cell communication
2022-01-05 | GSE149952 | GEO
Project description:The goals of this study are to harvest Rai1-deficient mouse brains from multiple tissues and timepoints and compare the transcriptome with their wild-type littermates. Methods: mRNA profiles from Rai1 conditional knockouts and wild-type mice were generated by deep sequencing, in duplicate using Illumina system. Conclusions: Our study suggests that Rai1 preferentially regulate genes involved in cell adhesion and neural projection.
2017-01-03 | GSE81206 | GEO
Project description:By generating knockin mice with an epitope tag on the C terminus of endogenous Rai1, we were able to perform in vivo ChIP-seq. Rai1 peaks co-localize with H3K4me3, Pol2, and Zfx peaks. Our data suggest that Rai1 is a transcription factor that interacts with chromatin, specifically in the promoter and enhancer regions.
2017-01-03 | GSE81204 | GEO