Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.
Abstract
Hematopoietic stem cells (HSC) reside within specialized microenvironments that undergo dynamic changes throughout development and aging to support HSC function. However, the evolving cell-cell communication networks within these niches remain largely unexplored. This study integrates single-cell RNA sequencing datasets to systematically characterize the HSC niche interactome from ontogeny to aging. We reconstructed single-cell atlases of HSC niches at different developmental stages, revealing stage-specific cellular compositions and interactions targeting HSC. During HSC maturation, our analysis identified distinct patterns of ligand-receptor interactions and signaling pathways that govern HSC emergence, expansion, and maintenance. HSC aging was accompanied by a decrease in supportive niche interactions, followed by an adaptive increase in interaction strength in old adult bone marrow. This complex aging process involved the emergence of interactions associated with inflammation, altered stem cell function, and a decline in the efficacy of key signaling pathways. Our findings provide a comprehensive understanding of the dynamic remodeling of the HSC niche interactome throughout life, paving the way for targeted interventions to maintain HSC function and promote healthy aging. This study offers valuable insights into the intricate cell-cell communication networks that govern HSC behavior and fate, with implications for hematological disorders and regenerative medicine.
The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.
Research summary
The paper is relevant to longevity research as it explores the dynamic changes in hematopoietic stem cell (HSC) niches throughout development and aging, which are crucial for understanding the underlying mechanisms of aging and potential interventions to maintain HSC function. The findings contribute important insights into the cell-cell communication networks that govern HSC behavior, which could have implications for promoting healthy aging and addressing age-related hematological disorders. However, while the study provides valuable information, it does not present a groundbreaking discovery that would significantly transform the field, hence the moderate impact score.
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