Hematopoietic stem cells (HSCs) exhibit functional alterations, such as reduced regenerative capacity and myeloid-biased differentiation, with age. The HSC niche, which is essential for the maintenance of HSCs, also undergoes marked changes with aging. However, it has been technically challenging to directly evaluate the contribution of niche aging to age-associated HSC alterations without niche-damaging myeloablation in HSC transplantation assays. We herein transplanted an excess of aged HSCs into young mice without preconditioning. Although aged HSCs successfully engrafted in the intact young bone marrow niche, they poorly regenerated downstream progenitors and exhibited persistent myeloid-biased differentiation, resulting in no significant functional rejuvenation. Transcriptome and methylome analyses revealed that the young niche largely restored the transcriptional profile of aged HSCs, but not their DNA methylation profiles. Therefore, the restoration of the young niche is insufficient for rejuvenating HSC functions, highlighting a key role for age-associated cell-intrinsic defects in HSC aging.
Skip Nav Destination
Close
Article navigation
Brief Definitive Report|
November 24 2020
Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche
Wakako Kuribayashi,
Wakako Kuribayashi
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Search for other works by this author on:
Motohiko Oshima,
Motohiko Oshima
Formal analysis
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Search for other works by this author on:
Naoki Itokawa,
Naoki Itokawa
Investigation
1
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Search for other works by this author on:
Shuhei Koide,
Shuhei Koide
Data curation, Formal analysis, Investigation
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Search for other works by this author on:
Yaeko Nakajima-Takagi,
Yaeko Nakajima-Takagi
Investigation
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Search for other works by this author on:
Masayuki Yamashita,
Masayuki Yamashita
Visualization, Writing - review & editing
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Search for other works by this author on:
Satoshi Yamazaki,
Satoshi Yamazaki
Conceptualization, Data curation, Formal analysis, Funding acquisition, Resources, Validation
3
Division of Stem Cell Biology, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan
4
Laboratory of Stem Cell Therapy, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Search for other works by this author on:
Bahityar Rahmutulla,
Bahityar Rahmutulla
Investigation
5
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for other works by this author on:
Fumihito Miura,
Fumihito Miura
Investigation
6
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Search for other works by this author on:
Takashi Ito,
Takashi Ito
Investigation
6
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Search for other works by this author on:
Atsushi Kaneda,
Atsushi Kaneda
Data curation, Supervision
5
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Search for other works by this author on:
Atsushi Iwama
Conceptualization, Funding acquisition, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing
1
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Correspondence to Atsushi Iwama: 03aiwama@ims.u-tokyo.ac.jp
Search for other works by this author on:
Wakako Kuribayashi
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Motohiko Oshima
Formal analysis
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Naoki Itokawa
Investigation
1
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Shuhei Koide
Data curation, Formal analysis, Investigation
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Yaeko Nakajima-Takagi
Investigation
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Masayuki Yamashita
Visualization, Writing - review & editing
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Satoshi Yamazaki
Conceptualization, Data curation, Formal analysis, Funding acquisition, Resources, Validation
3
Division of Stem Cell Biology, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan
4
Laboratory of Stem Cell Therapy, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
Bahityar Rahmutulla
Investigation
5
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Fumihito Miura
Investigation
6
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Takashi Ito
Investigation
6
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
Atsushi Kaneda
Data curation, Supervision
5
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
Atsushi Iwama
Conceptualization, Funding acquisition, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing
1
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
2
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Correspondence to Atsushi Iwama: 03aiwama@ims.u-tokyo.ac.jp
Received:
December 04 2019
Revision Received:
September 17 2020
Accepted:
October 19 2020
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding:
Japan Agency for Medical Research and Development
(JP20am0101103)
Ministry of Education, Culture, Sports, Science and Technology
(JP19H05653, JP26115002, JP19H05746)
© 2020 Kuribayashi et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2021) 218 (3): e20192283.
Article history
Received:
December 04 2019
Revision Received:
September 17 2020
Accepted:
October 19 2020
Citation
Wakako Kuribayashi, Motohiko Oshima, Naoki Itokawa, Shuhei Koide, Yaeko Nakajima-Takagi, Masayuki Yamashita, Satoshi Yamazaki, Bahityar Rahmutulla, Fumihito Miura, Takashi Ito, Atsushi Kaneda, Atsushi Iwama; Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche. J Exp Med 1 March 2021; 218 (3): e20192283. doi: https://doi.org/10.1084/jem.20192283
Download citation file:
Close
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
1,355
Views
0
Citations
Suggested Content
Advertisement