A deeper dive with Allen Yen
Understanding the molecular basis of neurodevelopmental disorders
“The massively parallel barcoding technology enabled cost-effective integration of multiple biological replicates per genotype at each time point, minimizing false discoveries and artifacts associated with snRNA-seq data sparsity.”Dr. Allen Yen Director, Research & Operations, Mark Therapeutics Developing gene therapies for Parkinson's Disease
Top-level highlights
412K
Total cells
33
Total samples
3
Genotypes profiled
Large-scale analysis across brain development
By profiling >400,000 mouse forebrain nuclei spanning MYT1L genotypes, developmental timepoints, and replicates, Dr. Yen and team used snRNA-seq to uncover how MYT1L impacts neurodevelopment.
Specific neuronal populations show unique vulnerability
Despite MYT1L 's broad neuronal expression, large-scale analysis revealed that certain cell types—particularly deep layer excitatory neurons at developmental stages E14 and P21—were uniquely susceptible to the mutation's effects, demonstrating cellular specificity that would have been missed with smaller studies.
Massive scale was essential for detecting subtle changes
MYT1L-related changes were extremely subtle, requiring robust statistical power that only large-scale single-cell sequencing could provide to capture the nuanced cellular alterations underlying this rare neurodevelopmental disorder.
Publication
MYT1L deficiency impairs excitatory neuron trajectory during cortical development
Allen Yen, Simona Sarafinovska, Xuhua Chen, Dominic D. Skinner, Fatjon Leti, MariaLynn Crosby, Jessica Hoisington-Lopez, Yizhe Wu, Jiayang Chen, Zipeng A. Li, Kevin K. Noguchi, Robi D. Mitra & Joseph D. Dougherty
Webinar snapshot
Using Single Cell Genomics to Investigate Epigenetic Gene Regulation — with Allen Yen
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