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Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells

Author

Listed:
  • Naoki Itokawa

    (Chiba University
    The University of Tokyo)

  • Motohiko Oshima

    (The University of Tokyo)

  • Shuhei Koide

    (The University of Tokyo)

  • Naoya Takayama

    (Chiba University Graduate School of Medicine)

  • Wakako Kuribayashi

    (Chiba University
    The University of Tokyo)

  • Yaeko Nakajima-Takagi

    (The University of Tokyo)

  • Kazumasa Aoyama

    (Chiba University
    The University of Tokyo)

  • Satoshi Yamazaki

    (The University of Tokyo
    University of Tsukuba)

  • Kiyoshi Yamaguchi

    (The University of Tokyo)

  • Yoichi Furukawa

    (The University of Tokyo)

  • Koji Eto

    (Chiba University Graduate School of Medicine
    Kyoto University)

  • Atsushi Iwama

    (Chiba University
    The University of Tokyo
    The University of Tokyo)

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.

Suggested Citation

  • Naoki Itokawa & Motohiko Oshima & Shuhei Koide & Naoya Takayama & Wakako Kuribayashi & Yaeko Nakajima-Takagi & Kazumasa Aoyama & Satoshi Yamazaki & Kiyoshi Yamaguchi & Yoichi Furukawa & Koji Eto & Ats, 2022. "Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30440-2
    DOI: 10.1038/s41467-022-30440-2
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    References listed on IDEAS

    as
    1. Anjali P. Kusumbe & Saravana K. Ramasamy & Tomer Itkin & Maarja Andaloussi Mäe & Urs H. Langen & Christer Betsholtz & Tsvee Lapidot & Ralf H. Adams, 2016. "Age-dependent modulation of vascular niches for haematopoietic stem cells," Nature, Nature, vol. 532(7599), pages 380-384, April.
    2. Anjali P. Kusumbe & Saravana K. Ramasamy & Tomer Itkin & Maarja Andaloussi Mäe & Urs H. Langen & Christer Betsholtz & Tsvee Lapidot & Ralf H. Adams, 2016. "Correction: Corrigendum: Age-dependent modulation of vascular niches for haematopoietic stem cells," Nature, Nature, vol. 539(7628), pages 314-314, November.
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    Cited by:

    1. Tsu-Yi Su & Julia Hauenstein & Ece Somuncular & Özge Dumral & Elory Leonard & Charlotte Gustafsson & Efthymios Tzortzis & Aurora Forlani & Anne-Sofie Johansson & Hong Qian & Robert Månsson & Sidinh Lu, 2024. "Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Hongna Zuo & Aiwei Wu & Mingwei Wang & Liquan Hong & Hu Wang, 2024. "tRNA m1A modification regulate HSC maintenance and self-renewal via mTORC1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Sudip Kumar Paul & Motohiko Oshima & Ashwini Patil & Masamitsu Sone & Hisaya Kato & Yoshiro Maezawa & Hiyori Kaneko & Masaki Fukuyo & Bahityar Rahmutulla & Yasuo Ouchi & Kyoko Tsujimura & Mahito Nakan, 2024. "Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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