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Hematopoietic Stem Cells: Molecular Insights into Homeostasis, Disease, and Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 29 January 2026 | Viewed by 119

Special Issue Editor


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Guest Editor
Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Hirakata 2-5-1 Shinmachi, Hirakata, Osaka 573-1010, Japan
Interests: hematopoietic stem cells; mesenchymal stem cells; machine learning

Special Issue Information

Dear Colleagues,

Hematopoietic stem cells (HSCs) sustain lifelong blood cell production through their capacity for self‑renewal and multilineage differentiation. Dysregulation of the molecular mechanisms that maintain HSC homeostasis can lead to hematological disorders such as bone marrow failure, clonal hematopoiesis, and leukemia. Moreover, aging-associated alterations in HSCs have been linked to impaired immune function and increased disease susceptibility in the elderly.

This Special Issue will focus specifically on the molecular mechanisms of HSC senescence and its contribution to the pathogenesis of age-related disorders. We invite cutting-edge research and reviews exploring the cellular and molecular drivers of HSC functional decline, such as DNA damage responses, epigenetic drift, and metabolic reprogramming. We particularly welcome studies on the interplay between clonal hematopoiesis, inflammation, and age-related diseases, and those employing single-cell or spatial transcriptomics to dissect HSC heterogeneity. From a translational perspective, this issue will also highlight the implications of HSC senescence in bone marrow failure and leukemia predisposition, aiming to foster new therapeutic strategies against age-related pathologies.

Dr. Yoshikazu Matsuoka
Guest Editor

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Keywords

  • hematopoietic stem cells (HSCs)
  • senescence
  • hematopoietic homeostasis
  • epigenetic drift
  • DNA damage responses
  • metabolic reprogramming
  • hematological disorders
  • inflammation
  • environmental stress

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Published Papers (1 paper)

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Research

18 pages, 3158 KB  
Article
Accumulation of Lymphoid Progenitors with Defective B Cell Differentiation and of Putative Natural Killer Progenitors in Aging Human Bone Marrow
by Laura Poisa-Beiro, Jonathan J. M. Landry, Aleksandr Cherdintsev, Michael Kardorff, Volker Eckstein, Laura Villacorta, Judith Zaugg, Anne-Claude Gavin, Vladimir Benes, Simon Raffel and Anthony D. Ho
Int. J. Mol. Sci. 2025, 26(21), 10467; https://doi.org/10.3390/ijms262110467 - 28 Oct 2025
Abstract
In animal models, elimination of the senescent cells in the hematopoietic stem cells (HSCs) compartment leads to the rejuvenation of hematopoiesis. Whether this treatment principle can be applied to the human system remains controversial. The identification of senescent cells in human bone marrow [...] Read more.
In animal models, elimination of the senescent cells in the hematopoietic stem cells (HSCs) compartment leads to the rejuvenation of hematopoiesis. Whether this treatment principle can be applied to the human system remains controversial. The identification of senescent cells in human bone marrow poses another major challenge. To address these questions, we have studied hematopoietic stem and progenitor cells (HSPCs, CD34+) from the bone marrow of 15 healthy human subjects (age range: 19–74 years). Single-cell RNA sequencing, functional transcriptome analysis, and development trajectory studies were performed. In a previous report, we demonstrated the accumulation of a senescent population in the aging HSC compartment. The present study focuses on the differences with age downstream in the lymphoid trajectory. While a reduction in B progenitors in the early lymphoid compartment can be confirmed, the accumulation of a lymphoid cluster downstream upon aging is novel and remarkable. This cluster comprises cells with a significant deficiency in B differentiation markers, as well as 9.4% cells with transcriptome signatures of memory-like natural killer (NK) progenitors. Applying our analysis algorithm to other human bone marrow datasets from the literature, we are able to validate the presence of this unique cluster in aged lymphoid progenitors. The accumulation of a population comprising cells defective in B differentiation potential, as well as cells with transcriptome features of memory-like NK progenitors represents a novel hallmark for senescence in the late development trajectory of human lymphoid compartment. Full article
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