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| Status |
Public on Sep 24, 2018 |
| Title |
Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The bone is essential for locomotion, calcium storage and harboring the hematopoietic stem cells (HSCs) that supply the body with mature blood cells throughout life. HSCs reside at the interface of the bone and bone marrow (BM), where active bone remodeling takes place. Although the cellular components of the BM niche have been characterized, little is known about its epigenetic regulation. Here we find that the histone methylation regulator PTIP (Pax interaction with transcription-activation domain protein-1) is required to maintain the integrity of the BM niche by promoting osteoclast differentiation. PTIP directly promotes chromatin changes required for the expression of Pparg (Peroxisome proliferator-activated receptor-γ), a transcription factor essential for osteoclastogenesis. PTIP deletion leads to a drastic reduction of HSCs in the BM and induces extramedullary hematopoiesis. Furthermore, exposure of acute myeloid leukemia cells to a PTIP-deficient BM microenvironment leads to a reduction in leukemia initiating cells (LICs) and increased survival upon transplantation. Taken together, our data identify PTIP as a novel epigenetic regulator of osteoclastogenesis that is required for the integrity of the BM niche to sustain both normal hematopoiesis and leukemia.
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| Overall design |
RNA-seq data from osteoclast progenitors isolated from fresh bone marrow of WT Mx-1Cre and Ptip flox/flox Mx-1Cre mice, two independent replicates.
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| Contributor(s) |
Das P, Veazey K, Van H, Kaushik S, Lin K, Lu Y, Ishii M, Kikuta J, Ge K, Nussenzweig A, Almeida Santos M |
| Citation(s) |
30297393 |
| Submission date |
Aug 09, 2018 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Margarida Almeida Santos |
| Organization name |
UT MD Anderson Cancer Center
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| Department |
Epigenetics and Molecular Carcinogenesis
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| Lab |
Santos Lab
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| Street address |
1515 Holcombe Blvd Mail code 1000
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| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA485240 |
| SRA |
SRP156849 |
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