Mecp2 duplication iNeurons RNAseq data tables

Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology. MECP2 duplication syndrome (MDS or MRXSL in OMIM; OMIM#300260) is one such CNV disorder caused by duplications spanning methyl CpG-binding protein 2 (MECP2) and other genes on Xq28. Using an antisense oligonucleotide (ASO) to normalize MECP2 dosage is sufficient to rescue abnormal neurological phenotypes in mouse models overexpressing MECP2 alone, implicating the importance of increased MECP2 dosage within CNVs of Xq28. However, because MDS CNVs span MECP2 and additional genes, we generated human neurons from multiple MDS patient-derived induced pluripotent cells (iPSCs) to evaluate the benefit of using an ASO against MECP2 in a MDS human neuronal context,. Importantly, we identified a signature of genes that is partially rescued upon ASO treatment and pinpointed genes sensitive to MeCP2 function and in models of Rett syndrome, a neurological disorder caused by loss of MeCP2 function. Furthermore, the signature contained genes that are aberrantly induced in unaffected control human neurons upon MeCP2 depletion, revealing gene expression programs sensitive to MeCP2 levels in human neurons. This repository contains the raw raws, processed reads, and processed RNA-seq analyses (DESeq2, limmavoom) from this study.

MDS_iNeurons_rawcounts_STAR.txt - raw counts from experiment

MDS_iNeurons_sample_information.txt - information describing sample conditions (genotype, ASO treatment, dose, etc).

SupplementalTable1.xlsx - DESeq2 and limmavoom results comparing MDS and unaffected controls; DESeq2 results comparing ASO treatments within a genotype

SupplementalTable2.xlsx - gene lists of genes altered by changes in MECP2 dosage

SupplementalTable3.xlsx - HOMER motif results of gene lists sensitive to MECP2 dosage