Your new experience awaits. Try the new design now and help us make it even better

EDITORIAL article

Front. Cell Dev. Biol., 07 July 2025

Sec. Stem Cell Research

Volume 13 - 2025 | https://doi.org/10.3389/fcell.2025.1607145

This article is part of the Research TopicAdvancements in Hematopoietic Stem Cell Proliferation and Self-Renewal MaintenanceView all 7 articles

Editorial: Advancements in hematopoietic stem cell proliferation and self-renewal maintenance

  • 1Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, United States
  • 2Netaji Subhas University of Technology Delhi, Delhi, India
  • 3Tokyo Metropolitan Institute of Medical Science Tokyo, Tokyo, Japan

Hematopoietic stem cells (HSCs) are the foundation of blood and immune system regeneration, with their self-renewing populations (SRPs) serving as a primary reservoir within the bone marrow (Rodriguez-Fraticelli et al., 2018). These cells replenish precursor populations and support the hierarchical development of myeloid, lymphoid, and erythroid intermediates, further differentiating into short-lived immune and blood cell lineages (Orkin and Zon, 2008). SRPs play a vital role in immune defense, contributing to responses against infections, cancer, and radiation-induced immunosuppression (Ross et al., 2024; Hollingsworth et al., 2023). Among SRPs, long-term culture-initiating cells (LTC-ICs) are essential in restoring hematopoietic function after radiation exposure (Rodriguez-Fraticelli et al., 2018; Orkin and Zon, 2008). These cells can regenerate depleted precursor and progenitor populations, making them invaluable for treating patients exposed to high radiation doses (Biermann and Reya, 2022). However, despite their therapeutic potential, direct transplantation of SRPs presents significant challenges due to the difficulty in mobilizing and harvesting them in sufficient quantities for clinical application (Williams et al., 2024; Burt et al., 2008). Traditional methods, such as direct bone marrow aspiration from the iliac crest or in vitro expansion, are invasive and have logistical constraints. Meanwhile, cytokine-driven expansion requires prohibitively high doses, making it financially and biologically unfeasible. This underscores the need for novel strategies to enhance SRP availability, including gene therapy, combination treatments with cytokines and small molecules, and innovative approaches to preserving their self-renewal capacity while maintaining stemness.

This research topic combines cutting-edge methodologies and protocols that advance HSC proliferation and self-renewal. This research topic fosters critical discussions on optimizing SRP expansion and sustainability by consolidating insights from established and emerging techniques. As the field progresses, continued research will be essential to unlocking the full therapeutic potential of these self-renewing HSCs, paving the way for advancements in regenerative medicine and immune system restoration. The review by Cox et al. explored the role of Lin28b, an RNA-binding protein, in HSC development and function. Lin28b is predominantly expressed in fetal hematopoietic stem and progenitor cells (HSPCs) and is crucial in regulating the transition from fetal to adult HSCs. This review highlights how Lin28b influences HSC expansion and differentiation during early development, providing valuable insights into potential strategies for enhancing ex vivo HSC expansion. By leveraging the regulatory mechanisms controlled by Lin28b, this study offers promising avenues for improving HSC self-renewal and advancing therapeutic applications in regenerative medicine. Jia et al. investigated the effects of Polo-like kinase 1 (PLK1) inhibition on erythroid differentiation using both in vitro and in vivo models. PLK1 inhibitors, specifically GSK461364 and BI6727, significantly suppress erythroid cell proliferation. This suppression led to G2/M phase cell cycle arrest, increased apoptosis in erythroid cells, and the formation of abnormally nucleated late-stage erythroblasts. These findings underscore the critical role of PLK1 in erythroid differentiation and suggest that its inhibition could negatively impact normal erythropoiesis. This has potential implications for therapeutic strategies targeting PLK1, particularly in balancing anti-proliferative effects against possible hematopoietic side effects. Shin et al. examine the role of the key transcription factor TAL1 in erythropoiesis. TAL1 overexpression enhances red blood cell (RBC) production from induced pluripotent stem cells (iPSCs). TAL1 significantly improves hematopoietic differentiation, increasing the yield of glycophorin A+/CD71+ cells and gamma hemoglobin levels. However, its overexpression reduces enucleation efficiency, posing a challenge in generating mature, transfusable RBCs. Morino-Koga and Yokomizo reviewed key signaling pathways and mechanisms essential for HSC development. They discuss the transition of hemogenic endothelium to HSPCs, emphasizing the roles of specific signaling molecules and transcriptional regulators such as Wnt, Notch, and BMP in regulating HSC proliferation, differentiation, and self-renewal. This review highlights the importance of the microenvironment, particularly niche cell interactions, in maintaining the HSC function. Understanding these mechanisms is essential for improving hematopoiesis and blood-related disorders therapies. Kitajima et al. investigated the role of the transcription factor Lhx2 in the ex vivo expansion of HSPCs derived from human iPSCs. This study explores how modifying Lhx2 activity enhances the proliferation and self-renewal of HSPCs, which is crucial for improving hematopoietic cell therapy. The findings provide insights into optimizing iPSC-based HSPC production for clinical applications, emphasizing the potential of manipulating key transcription factors to enhance stem cell yield. Luanpitpong et al. examined the role of O-GlcNAcylation, a post-translational modification in hematopoiesis. Editing OGT and OGA genes in human iPSCs reveals how O-GlcNAcylation influences HSC function and differentiation. This study provides a deeper understanding of the metabolic regulation of HSCs and identifies potential targets for therapeutic intervention. Collectively, these articles contribute significantly to the current understanding of HSC biology. They offer novel insights into the molecular mechanisms that regulate HSC proliferation and self-renewal, paving the way for advancements in regenerative medicine and treatments for hematological diseases.

Author contributions

PR: Methodology, Formal Analysis, Validation, Supervision, Data curation, Conceptualization, Writing – original draft, Investigation, Visualization, Writing – review and editing. GG: Formal Analysis, Validation, Writing – review and editing. TH: Writing – review and editing, Formal Analysis, Validation.

Funding

The author(s) declare that no financial support was received for the research and/or publication of this article.

Acknowledgments

The authors are thankful to the contributors to this research topic and the editorial support of Frontiers in Cell and Developmental Biology.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Biermann, M., and Reya, T. (2022). Hematopoietic stem cells and regeneration. Cold Spring Harb. Perspect. Biol. 14 (8), a040774. doi:10.1101/cshperspect.a040774

CrossRef Full Text | Google Scholar

Burt, R. K., Loh, Y., Pearce, W., Beohar, N., Barr, W. G., Craig, R., et al. (2008). Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. Jama 299 (8), 925–936. doi:10.1001/jama.299.8.925

PubMed Abstract | CrossRef Full Text | Google Scholar

Hollingsworth, B. A., Aldrich, J. T., Case Jr, C. M., DiCarlo, A. L., Hoffman, C. M., Jakubowski, A. A., et al. (2023). Immune dysfunction from radiation exposure. Radiat. Res. 200 (4), 396–416. doi:10.1667/rade-22-00004.1

CrossRef Full Text | Google Scholar

Orkin, S. H., and Zon, L. I. (2008). Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132 (4), 631–644. doi:10.1016/j.cell.2008.01.025

PubMed Abstract | CrossRef Full Text | Google Scholar

Rodriguez-Fraticelli, A. E., Wolock, S. L., Weinreb, C. S., Panero, R., Patel, S. H., Jankovic, M., et al. (2018). Clonal analysis of lineage fate in native haematopoiesis. Nature 553 (7687), 212–216. doi:10.1038/nature25168

PubMed Abstract | CrossRef Full Text | Google Scholar

Ross, J. B., Myers, L. M., Noh, J. J., Collins, M. M., Carmody, A. B., Messer, R. J., et al. (2024). Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity. Nature 628 (8006), 162–170. doi:10.1038/s41586-024-07238-x

CrossRef Full Text | Google Scholar

Williams, L. S., Williams, K. M., Gillis, N., Bolton, K., Damm, F., Deuitch, N. T., et al. (2024). Donor-derived malignancy and transplantation morbidity: risks of patient and donor genetics in allogeneic hematopoietic stem cell transplantation. Transpl. Cell. Ther. 30 (3), 255–267. doi:10.1016/j.jtct.2023.10.018

CrossRef Full Text | Google Scholar

Keywords: Hematopoietic stem cells (HSCS), Self-renewing populations (SRPs), Bone marrow-pathology, Long-term culture-initiating cells (LTC-ics), Hematopoietic stem and progenitor cells (HSPCs), Induced pluripotent stem cells (iPSCs), Self-renewal, Proliferation

Citation: Raghav PK, Gangenahalli G and Hara T (2025) Editorial: Advancements in hematopoietic stem cell proliferation and self-renewal maintenance. Front. Cell Dev. Biol. 13:1607145. doi: 10.3389/fcell.2025.1607145

Received: 07 April 2025; Accepted: 04 June 2025;
Published: 07 July 2025.

Edited and reviewed by:

Valerie Kouskoff, The University of Manchester, United Kingdom

Copyright © 2025 Raghav, Gangenahalli and Hara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Pawan Kumar Raghav, cHducmdodkBnbWFpbC5jb20=

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.