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Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis [ATAC-Seq]

UID: 10707

Author(s): Ott, Christopher J., Viny, Aaron David* * MSK affiliated

Description
Summary of the GEO: "Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation, however cohesin-mutant leukemias do not show genomic instability. We hypothesized reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Bi-allelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation, and revealed an absolute requirement for cohesin in hematopoietic stem cell function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose-dependency for cohesin in regulating chromatin structure and hematopoietic stem cell function.
ATAC-seq in murine c-kit+ cells for the following genotypes: Smc3 fl/+, Smc3 del/+, Flt3-ITD, Smc3 fl/del Flt3-ITD"
Subject of Study
Subject(s)
OncoTree Cancer Type(s)
Acute Myeloid Leukemia
Access via GEO

Raw and BED sequencing data.
Accession #: GSE73215

Access via SRA

OTHER sequence reads for 8 samples.
Accession #: SRP063874

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA296386

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Data Type
Equipment Used
Dataset Format(s)
SRA, TAR, BED, RAW
Dataset Size
7.5 Mb (TAR of BED), 19 Gb (SRA)
Data Catalog Record Updated
2023-12-07