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Series GSE262364 Query DataSets for GSE262364
Status Public on Apr 11, 2024
Title MYT1L deficiency impairs excitatory neuron trajectory during cortical development [E14]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary MYT1L is a neuron-specific transcription factor routinely used in fibroblast-to-neuron transdifferentiation. Furthermore, mutations that reduce MYT1L function are associated with autism. Likewise, 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, and the cumulative impact of haploinsufficiency on chromatin has been unclear. In this study, we profiled 277,698 nuclei from the forebrains of wild-type and MYT1L-deficient mice at two developmental stages: E14 at the peak of neurogenesis and P21, when neurogenesis is complete. We found that MYT1L deficiency had the strongest impact on deep layer excitatory neurons, specifically disrupting their trajectory of development and preventing arrival at a mature state. We also demonstrated that MYT1L acts primarily, but not exclusively, as a transcriptional repressor in these cell types, and most effects on gene expression are cell-autonomous. Furthermore, we developed and applied single-nucleus combinatorial indexing Calling Cards (sci-CC), an exponentially scalable method to simultaneously record gene expression and longitudinal enhancer activity in single nuclei over time. We find that the disruptions persist throughout neurodevelopment as excitatory neurons were disproportionately affected. 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.
 
Overall design For E14 samples, forebrains from mice were dissected and nuclei were harvested from 3 replicates each of MYT1L WT, Het, and KO mice. Males and females were collected and mixed for each genotype. Libraries were made using the Scale Biosciences Single Cell RNA Kit.
 
Contributor(s) Yen A, Chen X, Skinner D, Leti F, Wu Y, Chen J, Mitra RD, Dougherty JD
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Submission date Mar 25, 2024
Last update date Apr 12, 2024
Contact name Joseph D Dougherty
E-mail(s) jdougherty@wustl.edu
Organization name Washington University School of Medicine in St. Louis
Department Genetics
Street address 4370 Duncan Ave
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (18)
GSM8163923 E14 WT, replicate 1, run 1, snRNAseq
GSM8163924 E14 WT, replicate 2, run 1, snRNAseq
GSM8163925 E14 WT, replicate 3, run 1, snRNAseq
This SubSeries is part of SuperSeries:
GSE262368 MYT1L deficiency impairs excitatory neuron trajectory during cortical development
Relations
BioProject PRJNA1091600

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE262364_E14-MYT1L-forebrain.h5ad 6.2 Gb (ftp)(http) H5AD
GSE262364_RAW.tar 1.6 Gb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA

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