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Bulk transcriptome analysis of conditional MYT1L-mutant ESC-derived human induced neurons.

ABSTRACT: We examined the effect of heterozygous MYT1L deficiency in human induced neurons. Increased expression of genes with MYT1L binding motifs and activation of non-neuronal genes were observed in human neurons along with deregulation of autism-associated risk genes upon depletion of MYT1L.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171324 | GEO | 2023/02/14

REPOSITORIES: GEO

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			Action	DRS
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	GSE171324_human_bulk_deseq2_table.tsv.gz	Tabular
	GSE171324_human_bulk_norm_counts.tsv.gz	Tabular
	GSE171324_human_bulk_raw_counts.tsv.gz	Tabular

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Similar Datasets

Bulk transcriptome analysis of conditional MYT1L-mutant ESC-derived human induced neurons following Wnt and/or Notch inhibitor treatment.

Project description:We examined the effect of Wnt and/or Notch inhibition in the context of heterozygous MYT1L deficiency in human induced neurons. Increased expression of genes with MYT1L binding motifs and activation of non-neuronal genes were observed in human neurons along with deregulation of autism-associated risk genes upon depletion of MYT1L.

2023-02-14 | GSE217555 | GEO

Bulk transcriptome analysis of Myt1l mutant mouse neuron primary cultures.

Project description:We examined the effect of Myt1l deficiency in the neurons of mice. Homozygous Myt1l deficiency resulted in postnatal lethality, and mutant mice presented gene expression changes associated with developmental delays and resembled changes observed in autism spectrum disorder patients.

2023-02-14 | GSE217554 | GEO

MYT1L haploinsufficiency in human neurons and mice causes autism-associated phenotypes that can be reversed by genetic and pharmacologic intervention

Project description:MYT1L is an autism spectrum disorder (ASD)-associated transcription factor that is expressed in virtually all neurons throughout life. How MYT1L mutations cause neurological phenotypes and whether they can be targeted remains enigmatic. Here, we examine the effects of MYT1L deficiency in human neurons and mice. Mutant mice exhibit neurodevelopmental delays with thinner cortices, behavioural phenotypes, and gene expression changes that resemble those of ASD patients. MYT1L target genes, including WNT and NOTCH, are activated upon MYT1L depletion and their chemical inhibition can rescue delayed neurogenesis in vitro. MYT1L deficiency also causes upregulation of the main cardiac sodium channel, SCN5A, and neuronal hyperactivity, which could be restored by shRNA-mediated knockdown of SCN5A or MYT1L overexpression in postmitotic neurons. Acute application of the sodium channel blocker, lamotrigine, also rescued electrophysiologic defects in vitro and behaviour phenotypes in vivo. Hence, MYT1L mutation causes both developmental and postmitotic neurological defects. However, acute intervention can normalise resulting electrophysiological and behavioural phenotypes in adulthood.

2023-02-20 | PXD037867 | Pride

Bulk transcriptome analysis of conditional MYT1L-mutant ESC-derived human induced neurons.

Project description:Bulk transcriptome analysis of conditional MYT1L-mutant ESC-derived human induced neurons.

| PRJNA719236 | ENA

Bulk transcriptome analysis of Myt1l mutant mouse cortices across development.

Project description:We examined the effect of Myt1l deficiency in the cortices of mice during developement. Homozygous Myt1l deficiency resulted in postnatal lethality, and mutant mice presented gene expression changes associated with developmental delays and resembled changes observed in autism spectrum disorder patients.

2023-02-14 | GSE171325 | GEO

Brain transcriptome analysis of Myt1l heterozygote mutation mice (RNA-Seq I)

Project description:Myt1l is a transcription factor for neuronal induction and maintenance during development and Myt1l is highly implicated in autism spectrum disorder (ASD). Myt1l-mutant mice with a heterozygous deletion of exon 9 showed mild autistic-like behaviors (Social deficit and specific repetitive behaviors) and additional behavioral abnormalities including hyperactivity and anxiolytic-like behaviors in adult. To explore the molecular patterns and mechanisms underlying these behavioral abnormalities, we performed RNA-seq analysis of whole brain from wild-type and Myt1l-mutant mice longitudinally from pup stage (~P3) to juvenile (~P21) and adult (~P56) stages. Myt1l-mutant mice showed upregulations of chromosome- and chromatin-related genes and downregulations of synapse- and neurotransmitter-related genes during pup stage. However, from juvenile stage, Myt1l-mutant mice showed upregulations of extracellular matrix- and transporter-related genes and downregulations of mitochondria- and ribosome-related genes. In addition, Myt1l-mutant mice showed pro-ASD transcriptomic patterns on pup stage, but these patterns were reversed toward anti-ASD transcriptomic patterns from juvenile stages to adult stage as compensatory changes likely. These results suggest that the haploinsufficiency of Myt1l acutely alters the transcriptomic pattern into pro-ASD patterns and chronically compensates with the synapse maturation.

2025-06-17 | GSE185607 | GEO

Brain transcriptome analysis of Myt1l heterozygote mutation mice in different brain regions (RNA-Seq II)

Project description:Myt1l, a zinc-finger transcription factor, promotes neuronal differentiation and is implicated in autism spectrum disorders (ASD) and intellectual disability. However, it was previously unclear whether Myt1l promotes neuronal differentiation in vivo, how its deficiency leads to disease-related mouse phenotypes, and whether and how ASD-risk genes with strong embryonic and perinatal gene expression can yield strong adult-stage ASD-related phenotypes. Here, we report that Myt1l-heterozygous knockout (Myt1l-HT) mice display postnatal age-differential ASD-like phenotypes: Newborn Myt1l-HT mice show ASD-like transcriptomic changes involving suppressed neuronal and synaptic gene expression and suppressed right reflex. Juvenile Myt1l-HT mice display mixed ASD-like and reverse-ASD transcriptomic patterns and large normal behaviors, accompanying increased prefrontal excitatory synaptic transmission. However, adult Myt1l-HT mice show additional ASD-like transcriptomic changes involving astrocytic and microglial genes, along with behavioral deficits and excessive prefrontal inhibitory synaptic transmission. Therefore, Myt1l HT leads to newborn-stage ASD-like neuronal suppression, temporary juvenile normalization, and subsequent adult-stage ASD-like deficits.

2025-06-17 | GSE206714 | GEO

A MYT1L Syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation [RNA-Seq]

Project description:Human genetics have defined a new autism-associated syndrome caused by loss-of-function mutations in MYT1L, a transcription factor known for enabling fibroblast-to-neuron conversions. However, how MYT1L mutation causes autism, ADHD, intellectual disability, obesity, and brain anomalies is unknown. Here, we develop a mouse model of this syndrome. Physically, Myt1l haploinsufficiency causes obesity, white-matter thinning, and microcephaly in the mice, mimicking clinical phenotypes. Studies during brain development reveal disrupted gene expression, mediated in part by loss of Myt1l gene target activation, and highlight precocious neuronal differentiation as the mechanism for microcephaly. In contrast, adult studies reveal that mutation results in failure of transcriptional and chromatin maturation, echoed in disruptions in baseline physiological properties of neurons. This results in behavioral features including hyperactivity, hypotonia, and social alterations, with more severe phenotypes in males. Overall, these studies provide insight into the mechanistic underpinnings of this disorder and enable future preclinical studies.

2021-09-22 | GSE173926 | GEO

A MYT1L Syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation [ATAC-Seq]

2021-09-22 | GSE173588 | GEO

MYT1L deficiency impairs excitatory neuron trajectory during cortical development [P1]

Project description:Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a pro-neural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when neurons in the six cortical layers have been born, and P21 when neurogenesis is complete and neurons are maturing, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportions of cortical excitatory neurons. Changes in gene expression were concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.

2024-08-12 | GSE274102 | GEO

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