Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells

Naoki Itokawa, Motohiko Oshima, Shuhei Koide, Naoya Takayama, Wakako Kuribayashi, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Satoshi Yamazaki, Kiyoshi Yamaguchi, Yoichi Furukawa, Koji Eto and Atsushi Iwama ()
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Naoki Itokawa: Chiba University
Motohiko Oshima: The University of Tokyo
Shuhei Koide: The University of Tokyo
Naoya Takayama: Chiba University Graduate School of Medicine
Wakako Kuribayashi: Chiba University
Yaeko Nakajima-Takagi: The University of Tokyo
Kazumasa Aoyama: Chiba University
Satoshi Yamazaki: The University of Tokyo
Kiyoshi Yamaguchi: The University of Tokyo
Yoichi Furukawa: The University of Tokyo
Koji Eto: Chiba University Graduate School of Medicine
Atsushi Iwama: Chiba University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30440-2

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DOI: 10.1038/s41467-022-30440-2

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