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| Status |
Public on Jun 30, 2016 |
| Title |
Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, 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-/- MSPCs displayed impaired self-renewal and skewed differentiation-away from osteoblasts and favoring adipocytes. RNA-seq analysis reveals the altered expression of genes involved in cell proliferation, skeletal development and morphogenesis. Furthermore, gene set enrichment analysis showed a decreased gene expression of stem cell self-renewal signature,suggesting the role of Asxl1 in regulating the stemness of MSPCs. Importantly, introducing Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1-/- MSPCs. Our study unveils a pivotal role of ASXL1 in maintenance of MSPC functions and skeletal development.
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| |
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| Overall design |
Examination of mRNA profiles in wild type and Asxl1-/- MSPCs by deep sequencing
|
| |
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| Contributor(s) |
Zhang P, Xing C, Wang QF, Yang FC |
| Citation(s) |
27237378 |
| |
| Submission date |
Dec 08, 2015 |
| Last update date |
Dec 27, 2024 |
| Contact name |
Caiying Zhu |
| E-mail(s) |
zhucaiying@ihcams.ac.cn
|
| Phone |
13622053408
|
| Organization name |
Institute of Hematology and Blood Disease Hospital
|
| Street address |
Heping District, Nanjing Road, 288
|
| City |
Tianjin |
| ZIP/Postal code |
300020 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE75788 |
Loss of Asxl1 Alters Mesenchymal Stem Cell Fate through H3K4me3 |
|
| Relations |
| BioProject |
PRJNA305430 |
| SRA |
SRP067150 |
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