Abstract
Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.
Highlights
A key step in hematopoietic stem cell (HSC) aging research was achieved in 1996, revealing that Hematopoietic stem cells (HSCs) from old mice were only one-quarter as efficient as those from young mice at homing to and engrafting the bone marrow (BM) of irradiated recipients [1]
In the present review, we summarize the hallmarks of HSC aging in self-renewal, differentiation bias, and implantation ability
HSC aging is driven by multiple cell-intrinsic factors, including gene expression alterations, signaling pathway activation/repression, and epigenetic regulation
Summary
A key step in hematopoietic stem cell (HSC) aging research was achieved in 1996, revealing that HSCs from old mice were only one-quarter as efficient as those from young mice at homing to and engrafting the bone marrow (BM) of irradiated recipients [1]. Some novel age-associated chromatin markers in hematopoietic progenitors, including H3K23ac, H2BS14ph, and H3K9me, were observed at the single-cell level by highly multiplexed mass cytometry [85, 92] Hennrich et al revealed that the mRNA levels of age-increased glycolytic enzymes were higher in myeloid-primed hematopoietic stem/progenitor cells (HSPCs) than in lymphoid-primed HSPCs, whereas the transcript levels of age-unaffected enzymes were similar in both subsets [114] These results suggested that the lineage skewing of HSPCs toward myeloid differentiation upon aging was associated with the glycolytic pathway. Adelman et al observed a decrease in cycling-HSCs and lymphoid-primed multipotent progenitors during aging and identified 364 genes that are differentially expressed with age, such as Egr, Klf, and Jun [15] Overall, these single-cell analyses, summarized, helped to demonstrate the intrinsic molecular changes during HSC aging.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
