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| Status |
Public on Nov 12, 2015 |
| Title |
Combined loss of Tet1 and Tet2 promotes B-cell, but not myeloid malignancies in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
TET1/2/3 are methylcytosine dioxygenases regulating cytosine hydroxymethylation in the genome. Tet1 and Tet2 are abundantly expressed in HSC/HPCs and implicated in the pathogenesis of hematological malignancies. Tet2-deletion in mice causes myeloid malignancies, while Tet1-null mice develop B-cell lymphoma after an extended period of latency. Interestingly, TET1 and TET2 were often concomitantly down-regulated in acute B-lymphocytic leukemia. Here, we investigated the overlapping and non-redundant functions of Tet1/Tet2 in HSC maintenance and development of hematological malignancies using Tet1/2 double knockout (DKO) mice. DKO and Tet2-/- HSC/HPCs had overlapping and unique 5hmC and 5mC profiles and behaved differently. DKO mice exhibited strikingly decreased incidence and delayed onset of myeloid malignancies compared to Tet2-/- mice and in contrast developed lethal B-cell malignancies. Transcriptome analysis of DKO tumors revealed expression changes in many genes dysregulated in human B-cell malignancies, such as LMO2, BCL6 and MYC. These results highlight the critical roles of TET1 or TET2 individually and their cross-talks in the pathogenesis of hematological malignancies.
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| Overall design |
Given the role of Tet proteins in 5mC oxidation, we employed a previously established chemical labeling and affinity purification method coupled with high-throughput sequencing (hMe-Seal) to profile the genome-wide distribution of 5hmC, as well as methylated DNA immunoprecipitation (MeDIP) coupled with high-throughput sequencing (MeDIP-seq) to profile 5mC using BM LK cells purified from young WT, Tet2-/- and DKO mice (6-10 wks old).
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| Contributor(s) |
Jin P, Xu M |
| Citation(s) |
26586431 |
| Submission date |
Sep 30, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Peng Jin |
| E-mail(s) |
peng.jin@emory.edu
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| Phone |
4047273729
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| Organization name |
Emory University
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| Department |
Human Genetics
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| Lab |
Jin Lab
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| Street address |
615 Michael St., Rm 325
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| City |
Atlanta |
| State/province |
Georgia |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA297854 |
| SRA |
SRP064509 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE73611_RAW.tar |
32.6 Mb |
(http)(custom) |
TAR (of BED, FPKM_TRACKING) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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