bims-mithem 2026-02-22 papers

Issue of 2026–02–22
four papers selected by
Tim van Tienhoven, Erasmus Medical Center

Stem Cells Dev. 2026 Feb 16. 15473287261423853

Siglec-7 Links Mitochondrial Dynamics to Megakaryocytic Differentiation.

Su-Mei Lin, Shi Wu, Lung-Chih Yu, Yuh-Ching Twu.

Platelet biogenesis begins with the differentiation of hematopoietic stem cells (HSCs) into megakaryocytes (MKs) in the bone marrow, where mature MKs undergo endomitosis and ultimately release platelets. This program is tightly regulated by thrombopoietin, transcription factors, and metabolic cues, including mitochondrial reactive oxygen species and mitochondrial dynamics, which are now recognized as key drivers of megakaryopoiesis and thrombopoiesis. Sialic acid-binding immunoglobulin-like lectin (Siglec-7), a glycan-recognizing receptor, has been linked to mitochondrial dysfunction in natural killer cells, suggesting a potential role in modulating effector functions through oxidative phosphorylation. Here, using a phorbol 12-myristate 13-acetate (PMA)-induced K562 MK differentiation model, we examined how Siglec-7 expression relates to mitochondrial dynamics. Western blotting showed that mitochondrial dynamics-related proteins were markedly altered during PMA-induced differentiation, and confocal imaging revealed that Siglec-7+ MK-like cells displayed more elongated, highly branched mitochondrial networks than Siglec-7- one. In parallel, stored human platelets exhibited increased surface Siglec-7 expression. These findings identify Siglec-7 as a candidate regulator linking mitochondrial dynamics to MK differentiation and platelet function.

Keywords: Siglec-7; fission; fusion; megakaryocyte; mitochondrial dynamics

DOI: https://doi.org/10.1177/15473287261423853

Nat Commun. 2026 Feb 20.

Epigenetic profiling of hematopoietic stem cells from male mice identifies KDR and PU.1 as regulators of aging transcriptome and caloric restriction response.

Le Zong, Bongsoo Park, Ferda Tekin-Turhan, Wakako Kuribayashi, Mayuri Tanaka-Yano, Keefer Li, Isabel Beerman.

Caloric restriction (CR) provides anti-aging benefits but has also been reported to be associated with reduced immune function, and how hematopoietic stem cells (HSCs) potentially contribute to this decline remains unclear. Using lifelong and short-term CR in male mice, we found reducing the energy supply decreases total white blood cell production and shifts hematopoiesis towards myeloid and thrombo-erythroid lineages, prioritizing cells essential for survival (red blood cells, platelets, innate immune cells) over adaptive immunity. HSCs under CR enter cell cycle to support myeloid differentiation rather than self-renewal. Lifelong CR inhibits age-associated transcriptome changes in HSCs, though age-associated profiles appear shortly after ad libitum feeding. Epigenetic profiling identified KDR as a key CR response regulator, and Kdr knockdown in aged HSCs recapitulated the youthful transcriptome of lifelong CR HSCs. Finally, we show PU.1 acts as an intracellular regulator of CR response, controlling HSC self-renewal and differentiation through increased target gene binding under CR conditions.

DOI: https://doi.org/10.1038/s41467-026-69718-0

J Bone Miner Metab. 2026 Feb 19.

Multifunctional LepR⁺ skeletal stem/progenitor cells for bone and marrow homeostasis.

Karishma Madhusudan Desai, Toshihide Mizoguchi.

BACKGROUND: Bone is a multifunctional organ that provides structural support and hosts the bone marrow, a key site for hematopoiesis and systemic homeostasis. These dual features have long attracted the attention of both bone biologists and hematologists. Each field has pursued the identification of stem-like cells responsible for hard tissue formation and the regulatory microenvironment/niche that supports hematopoietic stem cells (HSCs), which give rise to all blood cell lineages. Converging advances in bone and hematopoietic biology have led to the identification of skeletal stem/progenitor cells (SSPCs), a multifunctional population that gives rise to osteolineage cells and serves as a principal component of the HSC niche. This landmark discovery was largely enabled by Cre/loxP-based genetic mouse models. Among them, the leptin receptor (LepR)-Cre system has become one of the most widely used tools in skeletal stem cell research worldwide.
OBJECTIVE: In this review, we summarize the historical background and recent advances in SSPC research, specifically LepR+ SSPCs, highlighting their function and lineage plasticity during development, adolescence, aging, and fracture healing. Advanced genetic labeling-based studies and single-cell transcriptomics unveiled the fate, dynamics and indispensible roles of LepR⁺ SSPCs under both homeostatic and pathological conditions.

Keywords: Aging; Bone development; Cell plasticity; Fracture healing; Hematopoietic stem cell niche; Leptin receptor; Lineage tracing analysis; Skeletal stem/progenitor cells

DOI: https://doi.org/10.1007/s00774-026-01698-z

Nat Immunol. 2026 Feb 17.

Single-cell multiomic atlas of healthy pediatric bone marrow reveals age-dependent differences in lineage differentiation driven by stromal signaling.

Evelyn S Hanemaaijer, Konradin F Müskens, Ireen J Kal, Li-Ting Chen, Brigit M Te Pas, Patrycja Fryzik, Nina Epskamp, Merel van der Meulen, Aleksandra K Balwierz, Akshaya K Saikumar Jayalatha, Marijn Scheijde-Vermeulen, Olaf Heidenreich, Tito Candelli, Wim J de Jonge, Thanasis Margaritis, Mirjam E Belderbos.

Childhood is a critical period for hematopoietic development and susceptibility to hematologic disease. Here we generated a multimodal single-cell atlas of healthy human bone marrow, capturing mRNA and surface protein expression in 90,710 cells, including over 20,000 hematopoietic stem and progenitor cells (HSPC) and mesenchymal stromal cells (MSC) from nine donors ranging from infancy to young adulthood (2-32 years). Young pediatric (YP) bone marrow (<10 years) was compositionally and molecularly distinct from adolescent and young adult (AYA) bone marrow (≥13 years), with hematopoietic output shifting from B cell dominance in YP bone marrow to myeloid and T cell bias in AYA bone marrow. Spatial transcriptomics of six bone marrow biopsies (0-23 years) confirmed these age-dependent changes. Two lymphoid progenitor (LyP) subsets regulated this lineage shift: CD127+ LyP cells with B cell-biased output were enriched before age 10, whereas CD127- LyP cells with combined lymphoid and myeloid features predominated thereafter. Stromal signaling showed corresponding age-dependent changes, with increased interleukin-7 production by bone marrow MSC in YP compared to AYA, indicating niche-mediated regulation of HSPC lineage potential during ontogeny. This single-cell atlas provides a comprehensive resource for understanding hematopoietic development and early-life origins of hematologic disease.

DOI: https://doi.org/10.1038/s41590-026-02422-9