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Series GSE118329 Query DataSets for GSE118329
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
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.
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.
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
Department Epigenetics and Molecular Carcinogenesis
Lab Santos Lab
Street address 1515 Holcombe Blvd Mail code 1000
City Houston
State/province Texas
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (4)
GSM3325413 Ptip flox/flox Mx-1Cre 1
GSM3325414 Ptip flox/flox Mx-1Cre 2
GSM3325415 WT Mx-1Cre 1
BioProject PRJNA485240
SRA SRP156849

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Supplementary file Size Download File type/resource
GSE118329_edgeR_cpm_effective_libsize.txt.gz 562.8 Kb (ftp)(http) TXT
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