bims-mithem 2026-07-12 papers

Issue of 2026–07–12
three papers selected by
Tim van Tienhoven, Erasmus Medical Center

J Clin Transl Res. 2025 Oct 29. 11(5): 50-68

Metabolomics of healthy hematopoietic stem cells and leukemic stem cells.

Gavin M Traber, Emely A Pacheco, Ansh Kumar, Edziu Franczak, Kelsey H Fisher-Wellman, Kathleen M Sakamoto.

Background. Hematopoietic stem cells (HSCs) reside in the bone marrow and are responsible for the life-long production of blood cells by balancing quiescence, self-renewal, and differentiation. A major feature distinguishing quiescent HSCs from their activated counterparts is a shift in the metabolic profile including changes in glycolytic flux and mitochondrial oxidative metabolism. Disruptions to HSC homeostasis can lead to hematologic diseases such as bone marrow failure or clonal hematopoiesis and even oncogenic transformation to form leukemic stem cells (LSCs). Like that of HSCs, LSCs retain stem-like characteristics but also gain features of malignancy including drug resistance and a hijacked metabolism that exhibit distinct metabolic profiles that can underlie their pathogenesis. The aim of this review is to summarize the key metabolic characteristics that distinguish healthy quiescent and active HSCs as well as oncogenic LSCs. Here we also explore the modern tools used to investigate the metabolome and how they can reveal novel metabolites, metabolic interactions and pathways, and targets for diagnosis or therapeutic intervention of hematologic diseases. Understanding and interrogating changes to the metabolic profiles of healthy and leukemic stem cells may lead to the development of innovative techniques, technologies, and therapeutics. In turn, these advances can be used for the identification, treatment, and prevention of hematologic disease. By better understanding their metabolome, therapies can be designed to target the unique metabolic pathways, dependencies, and resistance mechanisms of LSCs.

Keywords: hematopoietic stem cells; leukemic stem cells; metabolism; metabolomics

DOI: https://doi.org/10.36922/jctr025320053

Sci Prog. 2026 Jul-Sep;109(3):109(3): 368504261459907

Proteomic profiling reveals mitochondrial metabolic alterations in dexamethasone-induced neuronal differentiation.

Ekkaphot Khongkla, Jaturon Kwanthongdee, Banthit Chetsawang.

ObjectiveAs an in vitro model of catecholaminergic neurons, Cath.a Differentiated cells or CAD cells have been selected because of their direct origin in the mouse CNS and their ability to undergo inducible differentiation. Dexamethasone (DEX), a glucocorticoid receptor agonist, generates postmitotic and neurite-bearing CAD cells. Although the morphological differentiation of CAD cells induced by DEX has been well characterized, a comprehensive understanding of its proteomic profile and underlying pathways remains limited. Neuronal differentiation involves substantial remodeling of mitochondrial metabolic programs. However, the relationship between DEX-induced neuronal differentiation in CAD cells and mitochondrial metabolic state remains incompletely understood.MethodsIn this study, we applied a label-free quantitative SWATH-MS proteomic approach to investigate the protein expression in CAD cells upon differentiation.ResultsThe results of the proteomic analysis of 1,114 proteins associated with various GO terms, including neuronal differentiation and characteristics of brain-derived CAD cells, are shown. The data revealed the upregulation of proteins involved in mitochondria-associated metabolism and oxidative phosphorylation in DEX-differentiated cells compared with those in dividing cells, highlighting the role of mitochondrial metabolic changes during the neuronal differentiation of CAD cells. In addition, we identified proteins that were commonly expressed between the two neuronal differentiating protocols. A shared set of proteins involves electron transport, metabolic pathways, and DNA repair.ConclusionsThis study first highlights the proteomic signature and elucidates the key altered molecular pathways underlying DEX-induced neuronal differentiation in CAD cells.

Keywords: CAD cell line; SWATH-based proteomics; dexamethasone; metabolic reprogramming; neuronal differentiation; pathway annotation

DOI: https://doi.org/10.1177/00368504261459907

Res Sq. 2026 Jun 30. pii: rs.3.rs-10155437. [Epub ahead of print]

Aging reprograms the functional, epigenetic, and metabolic landscape of macrophages.

Manasa Suresh, Francisco Tapia Belmonte, Bryan T Weselman, Xintang Li, Marie Durr, Isabella Duchovny, Yanitza Gutierrez-Monsalve, Matias I Hepp, Satish Kumar R Noonepalle, Alexis Salas-Burgos, Alejandro Villagra.

Immuno-senescence is a dominant risk factor of chronic diseases, yet the impact of aging on macrophages remain understudied, despite their involvement in age-related conditions. Here, we define macrophage aging by integrating transcriptomic, epigenetic, metabolic, and functional analyses across the lifespan. Besides aging hallmarks, we uncovered progressive changes in macrophages, including reduced responsiveness to both inflammatory and anti-inflammatory cues and an imbalanced cytokine and chemokine secretory profile. This age-driven remodeling is supported by significant rewiring of epigenetic regulators, particularly histone-modifying genes, alongside coordinated shifts in metabolism toward lipid activation and trafficking at the expense of mitochondrial redox programs. Strikingly, these alterations differ between M1- and M2-like macrophages, indicating phenotype-specific aging trajectories. Functionally, aged macrophages exhibit enhanced phagocytic capacity, diminished migratory ability, and preserved antigen presentation. Together, our findings establish that aging does not simply impair macrophages; it drives an active, multi-layered reprogramming process, providing a framework to address inflammaging and age-associated diseases.

DOI: https://doi.org/10.21203/rs.3.rs-10155437/v1