Aging and Clonal Behavior of Hematopoietic Stem Cells
Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests tha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/1948 |
| _version_ | 1797479471771549696 |
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| author | Masayuki Yamashita Atsushi Iwama |
| author_facet | Masayuki Yamashita Atsushi Iwama |
| author_sort | Masayuki Yamashita |
| collection | DOAJ |
| description | Hematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. In this review, we summarize the current fate-mapping strategies that are used to track and visualize HSC clonal behavior during development or after stress. We then review the age-related changes in HSCs that can be inherited by daughter cells and act as a cellular memory to form functionally distinct clones. Altogether, we link aging of the hematopoietic system to HSC clonal evolution and discuss how HSC clones with myeloid skewing and low regenerative potential can be expanded during aging. |
| first_indexed | 2024-03-09T21:46:23Z |
| format | Article |
| id | doaj.art-c95a68ecd2bf45989da5b7ac55e116a3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:46:23Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c95a68ecd2bf45989da5b7ac55e116a32023-11-23T20:17:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234194810.3390/ijms23041948Aging and Clonal Behavior of Hematopoietic Stem CellsMasayuki Yamashita0Atsushi Iwama1Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai Minato-ku, Tokyo 108-8639, JapanDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai Minato-ku, Tokyo 108-8639, JapanHematopoietic stem cells (HSCs) are the only cell population that possesses both a self-renewing capacity and multipotency, and can give rise to all lineages of blood cells throughout an organism’s life. However, the self-renewal capacity of HSCs is not infinite, and cumulative evidence suggests that HSCs alter their function and become less active during organismal aging, leading ultimately to the disruption of hematopoietic homeostasis, such as anemia, perturbed immunity and increased propensity to hematological malignancies. Thus, understanding how HSCs alter their function during aging is a matter of critical importance to prevent or overcome these age-related changes in the blood system. Recent advances in clonal analysis have revealed the functional heterogeneity of murine HSC pools that is established upon development and skewed toward the clonal expansion of functionally poised HSCs during aging. In humans, next-generation sequencing has revealed age-related clonal hematopoiesis that originates from HSC subsets with acquired somatic mutations, and has highlighted it as a significant risk factor for hematological malignancies and cardiovascular diseases. In this review, we summarize the current fate-mapping strategies that are used to track and visualize HSC clonal behavior during development or after stress. We then review the age-related changes in HSCs that can be inherited by daughter cells and act as a cellular memory to form functionally distinct clones. Altogether, we link aging of the hematopoietic system to HSC clonal evolution and discuss how HSC clones with myeloid skewing and low regenerative potential can be expanded during aging.https://www.mdpi.com/1422-0067/23/4/1948hematopoietic stem cellsfate mappingagingclonal hematopoiesis |
| spellingShingle | Masayuki Yamashita Atsushi Iwama Aging and Clonal Behavior of Hematopoietic Stem Cells International Journal of Molecular Sciences hematopoietic stem cells fate mapping aging clonal hematopoiesis |
| title | Aging and Clonal Behavior of Hematopoietic Stem Cells |
| title_full | Aging and Clonal Behavior of Hematopoietic Stem Cells |
| title_fullStr | Aging and Clonal Behavior of Hematopoietic Stem Cells |
| title_full_unstemmed | Aging and Clonal Behavior of Hematopoietic Stem Cells |
| title_short | Aging and Clonal Behavior of Hematopoietic Stem Cells |
| title_sort | aging and clonal behavior of hematopoietic stem cells |
| topic | hematopoietic stem cells fate mapping aging clonal hematopoiesis |
| url | https://www.mdpi.com/1422-0067/23/4/1948 |
| work_keys_str_mv | AT masayukiyamashita agingandclonalbehaviorofhematopoieticstemcells AT atsushiiwama agingandclonalbehaviorofhematopoieticstemcells |