bims-mithem 2026-09-13 papers

Issue of 2026–09–13
three papers selected by
Tim van Tienhoven, Erasmus Medical Center

Exp Hematol. 2026 Sep 07. pii: S0301-472X(26)00538-2. [Epub ahead of print] 105905

Haematopoietic stem cell fitness mechanisms.

Yavor Bozhilov, Hugo Vassort, Adam C Wilkinson.

Haematopoietic stem cells (HSCs) are important for human health and clinical therapy. A heterogenous pool of HSCs sustain blood production through life by balancing self-renewal and multilineage differentiation. Aging is associated with a decline in the function of the HSC pool and haematopoietic perturbations. Additionally, aging correlates with clonal haematopoiesis, driven by the accumulation of genetic mutations in this long-lived cell population that can lead to altered cell function and ultimately to leukemic transformation. Alongside their natural role in sustaining haematopoiesis, healthy HSCs are also used clinically for their regenerative capacity in stem cell transplantation, where they reconstitute the entire adult blood system and can cure a range of blood disorders. Within these contexts, the term fitness is regularly used but often poorly defined. In this perspective, we summarise two distinct types of HSC fitness, clonal fitness and stem cell fitness. We go on to introduce mechanisms known to shape each and discuss the therapeutic implications for modulating HSC fitness mechanisms. TEASER ABSTRACT: This Perspective discusses two types of hematopoietic stem cell fitness, clonal fitness and stem cell fitness, and summarise mechanisms known to shape each and their therapeutic implications.

Keywords: Hematopoietic stem cell; clonal fitness; clonal hematopoiesis; stem cell fitness

DOI: https://doi.org/10.1016/j.exphem.2026.105905

Transplant Cell Ther. 2026 Sep 11. pii: S2666-6367(26)00707-4. [Epub ahead of print]

Integrated analysis of hematopoietic changes following heterochronic bone marrow transplantation between young and aged mice.

José Antonio Bejarano-García, Melanie Nufer, Rocío Caracuel, Teresa Caballero-Velázquez, Alfonso Rodríguez Gil, Alicia Jordano, Raquel Muñoz, José Ignacio Piruat, José Antonio Pérez-Simón.

BACKGROUND: aging is a multifactorial process characterized by progressive loss of tissue homeostasis and regenerative capacity, with haematopoiesis being profoundly affected. Age-associated changes in hematopoietic stem cells (HSCs) include increased frequency but reduced function, impaired self-renewal, and myeloid bias, driven by both intrinsic defects and extrinsic cues from the bone marrow (BM) niche. While heterochronic BM transplantation (hBMT) has been used to distinguish donor- versus niche-driven mechanisms, most studies have focused on isolated readouts under simplified conditions.
OBJECTIVE: to perform a systematic and descriptive analysis of hematopoietic reconstitution following hBMT in mice.
STUDY DESIGN: young and aged CD45.1 mouse BM cells were transplanted into lethally irradiated young or aged CD45.2 recipients mice, and hematopoietic output was evaluated six months later. Age-matched non-transplanted controls were included to contextualize aging trajectories.
RESULTS: the study confirm canonical features of hematopoietic aging, such as HSC accumulation, impaired lymphopoiesis, T cell memory skewing, and erythroid decline, but reveal that their expression after transplantation depends on the interplay of donor age, recipient environment, and procedural stress. Donor-intrinsic programs dominated the T cell compartment, driving naïve-to-memory conversion, PD1 upregulation, and Helios expression in regulatory T cells. By contrast, myeloid skewing and erythroid decline were dictated by recipient age, underscoring environmental influence. Importantly, the transplantation process itself imposed selective lineage stress, disproportionately affecting B cell development and conventional T cells, while sparing regulatory T cells and most myeloid compartment.
CONCLUSIONS: together, this study provides a descriptive phenotypic atlas of post-transplant haematopoiesis, highlighting detrimental effects of the transplantation process itself and lineage- and tissue-specific vulnerabilities.

Keywords: Aging; Hematopoietic Stem Cell Transplantation (HSCT); Heterochronic Bone Marrow Transplantation (BMT); Immune aging

DOI: https://doi.org/10.1016/j.jtct.2026.09.011

Blood. 2026 Sep 09. pii: blood.2025032368. [Epub ahead of print]

Rare Hematopoietic Stem Cells resilient to infection-induced stress sense yet withstand inflammation.

Hematopoietic stem cells (HSCs) sustain lifelong hematopoiesis as their progeny differentiate into all blood cell lineages. Homeostatic HSCs are mostly quiescent and only rarely divide, however their proliferation and differentiation rates can be modulated by external factors. Acute and chronic infections from a wide range of pathogens are known to challenge HSCs at the population level, being forced to respond to inflammation-mediated organismal demand to replenish the myeloid cell pool. However, less is known about the degree of heterogeneity in the HSCs' response to inflammation at the single cell level. Here, using a natural murine malaria model and an NHS-ester biotin dilution assay we identify two subsets of HSCs, BiotinLo and BiotinHi, with distinct proliferation kinetics. Using combined functional, single-cell transcriptomics and phenotypic analyses, we uncover that BiotinHi HSCs remain highly functional despite expressing strong interferon response signatures. These resilient HSCs are more poised to enter cell cycle than control HSCs, but do not divide. They maintain less active mitochondria and express higher levels of CD74 and MHC-II. Additionally, they express higher levels of integrin β2/CD18, which suggest they may have specific interactions with the bone marrow microenvironment. Similar patterns of NHS-ester biotin dilution were elicited by LPS and poly (I:C) challenges. These findings highlight previously unmeasured heterogeneity in the response of HSCs to acute infection-induced inflammation and demonstrate that a likely reserve pool of HSCs remains highly functional during Plasmodium infection not because cells are shielded, but because they maintain a stemness associated metabolic profile despite effectively sensing inflammation.

DOI: https://doi.org/10.1182/blood.2025032368