Myelodysplastic syndrome (MDS), a largely incurable hematological malignancy, is derived from aberrant clonal hematopoietic stem/progenitor cells (HSPCs) that persist after conventional therapies. Defining the mechanisms underlying MDS HSPC maintenance is critical for developing MDS therapy. The deacetylase SIRT1 regulates stem cell proliferation, survival, and self-renewal by deacetylating downstream proteins. Here we show that SIRT1 protein levels were downregulated in MDS HSPCs. Genetic or pharmacological activation of SIRT1 inhibited MDS HSPC functions, whereas SIRT1 deficiency enhanced MDS HSPC self-renewal. Mechanistically, the inhibitory effects of SIRT1 were dependent on TET2, a safeguard against HSPC transformation. SIRT1 deacetylated TET2 at conserved lysine residues in its catalytic domain, enhancing TET2 activity. Our genome-wide analysis identified cancer-related genes regulated by the SIRT1/TET2 axis. SIRT1 activation also inhibited functions of MDS HSPCs from patients with TET2 heterozygous mutations. Altogether, our results indicate that restoring TET2 function through SIRT1 activation represents a promising means to target MDS HSPCs.
Pubmed ID: 30146412 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Human SIRT1
View all literature mentionsThis polyclonal targets HA tag - ChIP Grade
View all literature mentionsThis polyclonal targets acetyl Lysine antibody - ChIP Grade
View all literature mentionsThis polyclonal targets Histone H4
View all literature mentionsThis monoclonal targets 5-Hydroxymethylcytosine / 5-hmC
View all literature mentionsThis polyclonal targets TET2
View all literature mentionsThis monoclonal targets p300 CT
View all literature mentionsThis monoclonal targets Histone H3 (D1H2) XP Rabbit mAb
View all literature mentionsThis polyclonal targets Acetyl-p53 (Lys382)
View all literature mentionsThis monoclonal targets Hsp90aa1
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD117 (c-Kit)
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets CD127
View all literature mentionsThis monoclonal targets TER-119
View all literature mentionsThis monoclonal targets CD41a
View all literature mentionsThis monoclonal targets Ly-6G/Ly-6C
View all literature mentionsThis monoclonal targets NK1.1
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets IgM
View all literature mentionsThis monoclonal targets CD45R (B220)
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD15
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsThis monoclonal targets CD38
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets CD235a (Glycophorin A)
View all literature mentionsThis monoclonal targets CD7
View all literature mentionsThis monoclonal targets CD10
View all literature mentionsThis monoclonal targets TER-119
View all literature mentionsThis monoclonal targets Ly-6A/E
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CD71
View all literature mentionsThis monoclonal targets CD33
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD2
View all literature mentionsThis monoclonal targets CD3
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Mus musculus with name B6(Cg)-Tet2tm1.2Rao/J from IMSR.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsA collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsImaging software that works with G:BOX Chemi and PXi imaging systems to automatically or manually capture images. GeneSys also includes a database containing information about applications such as fluorescence, chemiluminescence and chemifluorescence.
View all literature mentionsMolecular biology software for visualizing and documenting gene constructs for InFusion cloning, Gibson assembly, restriction cloning, PCR, and mutagenesis.
View all literature mentions