We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells.
- Authors
Itokawa, Naoki; Oshima, Motohiko; Koide, Shuhei; Takayama, Naoya; Kuribayashi, Wakako; Nakajima-Takagi, Yaeko; Aoyama, Kazumasa; Yamazaki, Satoshi; Yamaguchi, Kiyoshi; Furukawa, Yoichi; Eto, Koji; Iwama, Atsushi
- Abstract
Hematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here, we present an integrated analysis of transcriptome and chromatin accessibility of aged HSCs and downstream progenitors. Alterations in chromatin accessibility preferentially take place in HSCs with aging, which gradually resolve with differentiation. Differentially open accessible regions (open DARs) in aged HSCs are enriched for enhancers and show enrichment of binding motifs of the STAT, ATF, and CNC family transcription factors that are activated in response to external stresses. Genes linked to open DARs show significantly higher levels of basal expression and their expression reaches significantly higher peaks after cytokine stimulation in aged HSCs than in young HSCs, suggesting that open DARs contribute to augmented transcriptional responses under stress conditions. However, a short-term stress challenge that mimics infection is not sufficient to induce persistent chromatin accessibility changes in young HSCs. These results indicate that the ongoing and/or history of exposure to external stresses may be epigenetically inscribed in HSCs to augment their responses to external stimuli. Haematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here the authors demonstrate that differentially accessible regions in aged HSC chromatin are enriched for stress-responsive enhancers and act as an epigenetic hub to augment transcriptional responses of aged HSCs to external stimuli.
- Subjects
CHROMATIN; TRANSCRIPTION factors; EPIGENETICS
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-30440-2