GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE223456 Query DataSets for GSE223456
Status Public on Feb 22, 2023
Title Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3 [scRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigated the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice resulted in restructuring of the chromatin architecture. This led to an ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern. Artificial repositioning of the AER-specific enhancers of Fgf8 was sufficient to induce misexpression of Lbx1 and Btrc. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression and dosage in the developing limb. Our results reveal new insights into the molecular mechanism underlying SHFM3 and provide novel conceptual framework for how genomic rearrangements can cause gene misexpression and disease.
Overall design We performed scRNA-seq to investigate the effect of the SHFM3-associated duplication on gene expression specifically in the AER cell cluster.
Contributor(s) Cova G
Citation(s) 36928426
Submission date Jan 22, 2023
Last update date May 24, 2023
Contact name Giulia Cova
Organization name Max Planck Institute
Street address 63-73 Ihnestrasse
City Berlin
ZIP/Postal code 14195
Country Germany
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (6)
GSM6956533 scRNAseq-mm-Wt-HL-E115-Rep1-L20666
GSM6956534 scRNAseq-mm-Dup-HL-E115-Rep1-L20667
GSM6956535 scRNAseq-mm-G4-FL-E115-Rep1-L27830
This SubSeries is part of SuperSeries:
GSE197404 Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3
BioProject PRJNA926342

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
GSE223456_scRNAseq-barcodes.tsv.gz 32.1 Kb (ftp)(http) TSV
GSE223456_scRNAseq-cellmetadata.tsv.gz 432.1 Kb (ftp)(http) TSV
GSE223456_scRNAseq-genes_ids.tsv.gz 49.1 Kb (ftp)(http) TSV
GSE223456_scRNAseq-matrix-counts.mtx.gz 55.9 Mb (ftp)(http) MTX
GSE223456_scRNAseq_FL_G4_Inv_mm_barcodes.tsv.gz 105.9 Kb (ftp)(http) TSV
GSE223456_scRNAseq_FL_G4_Inv_mm_counts.mtx.gz 171.9 Mb (ftp)(http) MTX
GSE223456_scRNAseq_FL_G4_Inv_mm_features.tsv.gz 52.6 Kb (ftp)(http) TSV
GSE223456_scRNAseq_HL_G4_Inv_mm_features.tsv.gz 55.4 Kb (ftp)(http) TSV
GSE223456_scRNAseq_HL_G4_Inv_mm_mm_barcodes.tsv.gz 66.3 Kb (ftp)(http) TSV
GSE223456_scRNAseq_HL_G4_Inv_mm_mm_counts.mtx.gz 107.5 Mb (ftp)(http) MTX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap