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| Status |
Public on Dec 08, 2018 |
| Title |
Loss of Asxl1 Alters Mesenchymal Stem Cell Fate through H3K4me3 [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome (BOS), a disease with severe developmental defects and early childhood fatality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models, we found that Asxl1 global loss or conditional deletion in osteoblasts and their progenitors in mice leads to significant bone loss and markedly decreased numbers of marrow mesenchymal stem/progenitor cells (MSPCs) compared with wild-type (WT) littermates. Asxl1 null MSPCs display impaired self-renewal and skewed differentiation from osteoblasts towards adipocytes. ChIP-seq data identified that ASXL1 and H3K4me3 co-occupy the promoter regions of genes critical for MSPC self-renewal. Loss of Asxl1 diminished the genome enrichment of H3K4me3. Combined analysis of RNA-seq and ChIP-seq data revealed that Asxl1 loss in MSPCs altered the expression of ASXL1/H3K4me3 target genes controlling self-renewal/lineage commitment. Our study unveil a pivotal role of ASXL1 in H3K4me3-associated bone homeostasis
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| Overall design |
Identification of ASXL1 binding profile in WT MSPCs and examination of 3 different histone modifications in WT and Asxl1-/- MSPCs.
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| Contributor(s) |
Zhang P, Xing C, Wang Q, Yang F |
| Citation missing |
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| |
| Submission date |
Dec 08, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Caiying Zhu |
| E-mail(s) |
zhucaiying@ihcams.ac.cn
|
| Phone |
13622053408
|
| Organization name |
Institute of Hematology & Blood Diseases Hospital
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| Street address |
NO. 288 Nanjing Road, Heping District, Tianjin
|
| City |
Tianjin |
| ZIP/Postal code |
300020 |
| Country |
China |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE75788 |
Loss of Asxl1 Alters Mesenchymal Stem Cell Fate through H3K4me3 |
|
| Relations |
| BioProject |
PRJNA305431 |
| SRA |
SRP067149 |
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