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Series GSE162659 Query DataSets for GSE162659
Status Public on Dec 05, 2020
Title Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells (EZH2_KO_HSC)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Epigenetic alterations are one of the hallmarks of HSC aging, and profiling of DNA methylation and histone modifications has provided potential mechanisms that contribute to HSC aging. Chromatin accessibility reflects a comprehensive transcriptional network operating in cells; however, it has not yet been investigated in HSC aging. Here we performed an integrated analysis of aged HSCs on transcriptome, chromatin accessibilities, and histone modifications. Alterations in chromatin accessibility preferentially took place in HSCs with aging, the cells at the top of hematopoietic hierarchy, suggesting that the age-associated alterations in chromatin accessibility are memorized in HSCs and are inherited to downstream progenitor cells. However, most genes with differentially accessible regions (DARs) were not actively transcribed and kept poised for activation in aged HSCs. Motifs of ATF/CREB, STAT, and CNC family transcription factors were significantly enriched at DARs in aged HSCs. These transcription factors are activated in response to external stresses such as cytokine and inflammation signals and oxidative stresses, suggesting that the long-term exposure to such stress signals have changed chromatin accessibility in HSCs to augment responses by such trained HSCs to subsequent stimuli. In contrast, aged HSC-specific gene expression occurred mainly at gene loci with poised accessible regions but not DARs without accompanying drastic chromatin reorganization, suggesting that altered cell-extrinsic stimuli or signals from aged niche largely account for this process. Our findings provide key epigenetic molecular insights into HSC aging and serve as a reference for future analysis. 
Overall design RNA-seq of Ezh2 knock out HSCs
Contributor(s) Itokawa N, Oshima M, Kuribayashi W, Takayama N, Koide S, Nakajima-Takagi Y, Kazumasa A, Yamazaki S, Eto K, Iwama A
Citation(s) 35577813
Submission date Dec 04, 2020
Last update date May 17, 2022
Contact name Atsushi Iwama
Organization name The Institute of Medical Science, The University of Tokyo
Department Center for Stem Cell Biology and Regenerative Medicine
Lab Division of Stem Cell and Molecular Medicine
Street address 4-6-1, Shirokanedai
City Minato-ku
State/province Tokyo
ZIP/Postal code 108-8639
Country Japan
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (2)
GSM4956335 WT_HSC
GSM4956336 Ezh2 KO HSC
This SubSeries is part of SuperSeries:
GSE162662 Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells
BioProject PRJNA682587
SRA SRP295871

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Supplementary file Size Download File type/resource
GSE162659_RAW.tar 190.0 Kb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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