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Series GSE231933 Query DataSets for GSE231933
Status Public on May 01, 2024
Title The chromatin remodeling factor Arid1a cooperates with Jun/Fos to promote osteoclastogenesis by epigenetically upregulating Siglec15 expression
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow?derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell?cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid?binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.
 
Overall design Comparison of gene expression profiles and chromatin accessibility during osteoblast differentiation after Arid1a knockout. *Submitters did not provide the processed data for ATAC-Seq and CUT&Tag.
 
Contributor(s) Zhang Y, Sun H, Huang F, Shen L, Ye Z
Citation(s) 38477755
Submission date May 08, 2023
Last update date May 07, 2024
Contact name Zhaoming Ye
E-mail(s) yezhaoming@zju.edu.cn
Organization name The Second Affiliated Hospital, Zhejiang University School of Medicine
Street address 88 jiefang road
City hangzhou
ZIP/Postal code 310031
Country China
 
Platforms (2)
GPL21273 HiSeq X Ten (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (37)
GSM7306238 wt_0d_RNAseq_rep1
GSM7306239 wt_0d_RNAseq_rep2
GSM7306240 wt_2d_RNAseq_rep1
Relations
BioProject PRJNA970261

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Supplementary file Size Download File type/resource
GSE231933_RAW.tar 38.6 Mb (http)(custom) TAR (of BW)
GSE231933_RNAseq_gene_expression.xlsx 3.2 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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