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Series GSE194170 Query DataSets for GSE194170
Status Public on Jul 31, 2022
Title PU.1-dependent enhancer inhibition separates clonal hematopoiesis from malignant transformation (oxBS-Seq)
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Hematopoietic stem cells sustain life-long blood production. While they are the known cellular origin of aging-associated myeloid malignancies, such as acute myeloid leukemia (AML), mechanisms driving their malignant transformation have remained elusive. Epigenetic dysregulation following acquired loss-of-function mutations of DNA methyl-cytosine dioxygenase Ten-Eleven Translocation-2 (TET2) occurs frequently in the elderly leading to cytosine hypermethylation in and around DNA binding sites of master transcription factors, including PU.1. Here we show that Tet2 deficient hematopoietic stem and progenitor cells (HSPC) undergo malignant transformation upon compromised PU.1 gene regulation. Leukemic stem and progenitor cells show hypermethylation at PU.1 binding sites and fail to activate PU.1-depenent myeloid enhancers, and are hallmarked by a defined signature of impaired genes shared with human AML. Our study demonstrates that Tet2 and PU.1 cooperate in suppressing leukemogenesis in HSPC and establishes a methylation sensitive PU.1-dependent gene network as a unifying feature in acute myeloid leukemia.
 
Overall design oxidative bisulfite sequencing of cKit+ HSPC purified from UREHETTet2HET and UREHETTet2KO mice and age-matched controls
 
Contributor(s) Aivalioti MM, Pradhan K, Will B
Citation(s) 35820129
Submission date Jan 21, 2022
Last update date Nov 01, 2022
Contact name Britta Will
E-mail(s) britta.will@einsteinmed.edu
Organization name Albert Einstein College of Medicine
Department Cell Biology
Street address 1300 Morris Park Avenue, Chanin Bldg., Rm. #401
City Bronx
State/province NY
ZIP/Postal code 10461
Country USA
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (16)
GSM5830058 URE+/+;Tet2+/+_BS1
GSM5830059 UREΔ/+;Tet2+/+_BS2
GSM5830060 URE+/+;Tet2+/-_BS3
This SubSeries is part of SuperSeries:
GSE191053 PU.1-dependent enhancer inhibition separates Tet2 deficient clonal hematopoiesis from malignant transformation
Relations
BioProject PRJNA799349

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE194170_RAW.tar 67.6 Gb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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