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Series GSE230235 Query DataSets for GSE230235
Status Public on May 11, 2023
Title Pre-Hypertrophic Chondrogenic Enhancer Landscape of Limb and Axial Skeleton Development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The precisely orchestrated differentiation of chondrocytes during skeleton development is a critical determinant of human height and body shape. Disruptions of this process can cause severe skeletal abnormalities. The ultimate size and shape of each of over 200 bones depends on the intricate spatiotemporal regulation of chondrogenic and chondrocyte differentiation genes, but the genomic architecture coordinating these events remains poorly defined. Here we provide a comprehensive map of transcriptional enhancers specifically active in chondrocytes and show that they provide a mechanistic framework through which noncoding genetic variants can influence human stature. We isolated limb and trunk fetal chondrocytes from mice with a Col2a1 fluorescent regulatory sensor and used RNA-seq to identify 780 genes that are specifically expressed during chondrogenesis. To create cell type-specific enhancer maps, we performed ATAC-seq to map open chromatin regions and ChIP-seq for H3K27ac, an enhancer-associated histone modification, and identified 2'704 putative chondrogenic enhancer regions. Most of these enhancers (74%) showed pan-chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. We found that chondrogenic enhancers are enriched for the binding of several chondrogenic transcription factors including SOX9. Moreover, we find that genetic variation overlapping chondrogenic enhancers explains a higher fraction of the heritability of human adult height than the one overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3, Col2a1, Hhip and, Nkx3-2 loci each exhibited a significant reduction of cognate gene expression, therefore demonstrating their functional importance. This data provides a comprehensive mapping of the chondrogenic enhancer repertoire, paving the way to interpreting the role of non-coding sequence polymorphisms in phenotypic variation and bone diseases.
 
Overall design Refer to individual Series
 
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Submission date Apr 21, 2023
Last update date Mar 02, 2024
Contact name Guillaume Andrey
E-mail(s) guillaume.andrey@unige.ch
Phone +41223795703
Organization name University of Geneva
Department Department of Genetic Medicine and Development
Street address Rue Michel-Servet 1
City Geneva
ZIP/Postal code 1211
Country Switzerland
 
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (61)
GSM7207908 scRNAseq-L-E145-Col2a1GFP
GSM7207909 RNAseq-L-E145-Col2a1GFP-GFPp-R1
GSM7207910 RNAseq-L-E145-Col2a1GFP-GFPp-R2
This SuperSeries is composed of the following SubSeries:
GSE230231 Pre-Hypertrophic Chondrogenic Enhancer Landscape of Limb and Axial Skeleton Development [scRNA-seq]
GSE230232 Pre-Hypertrophic Chondrogenic Enhancer Landscape of Limb and Axial Skeleton Development [RNA-seq]
GSE230233 Pre-Hypertrophic Chondrogenic Enhancer Landscape of Limb and Axial Skeleton Development [ATAC-seq]
Relations
BioProject PRJNA958096

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
GSE230235_RAW.tar 7.1 Gb (http)(custom) TAR (of BW, NARROWPEAK)
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