| Accession |
PRJCA000236 |
| Title |
Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell |
| Relevance |
Model organism |
| Data types |
Transcriptome or Gene expression
|
| Organisms |
Mus musculus
|
| Description |
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. |
| Sample scope |
Monoisolate |
| Release date |
2016-05-19 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 27237378
|
Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell, Leading to Bohring-Opitz-like Syndrome in Mice.
|
Stem Cell Reports
|
10.1016/j.stemcr.2016.04.013
|
2016
|
|
|
| Biomaterial provider |
Feng-Chun Yang |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Institutes of Health
|
|
CA172408
|
CA172408
|
| National Institutes of Health
|
|
CA185751
|
CA185751
|
| National Institutes of Health
|
|
HL112294
|
HL112294
|
| National Natural Science Foundation of China (NSFC)
|
|
81270612
|
81270612
|
| Chinese Academy of Sciences (CAS)
|
|
153F11KYSB20150013
|
153F11KYSB20150013
|
|
|
| Accessions in other database |
| Accession |
Database name |
| GSE75787
|
NCBI
|
|
|
| External link |
|
| Submitter |
Fuhong
He (hefh@big.ac.cn)
|
| Organization |
Beijing Institute of Genomics, Chinese Academy of Sciences |
| Submission date |
2016-05-19 |
