(Metabolome analysis data): Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway
UID: 10619
Publisher(s): The Institute of Medical Science- Description
- Description from MassIVE: Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs). HSCs expressing ASXL1-MT display competitive disadvantage after transplantation. Nevertheless, in genetic mosaic mouse model, they acquire clonal advantage during aging, recapitulating CH in humans. Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT. Overactive Akt/mTOR signaling induced by ASXL1-MT results in aberrant proliferation and dysfunction of HSCs associated with age-related accumulation of DNA damage. Treatment with an mTOR inhibitor rapamycin ameliorates aberrant expansion of the HSC compartment as well as dysregulated hematopoiesis in aged ASXL1-MT KI mice. Our findings suggest that ASXL1-MT provokes dysfunction of HSCs, whereas it confers clonal advantage on HSCs over time, leading to the development of CH."
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Access via MassIVE
RAW files of Metabolome analysis
Accession #: MSV000086816 - Access Restrictions
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Free to All
- Access Instructions
- MassIVE (Mass Spectroscopy Interactive Virtual Environment) is a community resource developed by the NIH-funded Center for Computational Mass Spectrometry to promote the global, free exchange of mass spectrometry data. An account must be created to use MassIVE Workflows which enables files conversion and analysis. Files may be downloaded through an ftp link.
- DOI
- 10.25345/C5NJ66
- Associated Publications
- Equipment Used
- Dataset Format(s)
- RAW, mzML
- Dataset Size
- 1 GB (RAW), 300 MB (mzML)
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