Molecular biology reports · 2025
The crucial role of circadian synchronization in bone marrow adipose tissue mesenchymal stem cells: insights into pathogenesis in Fanconi anemia and acute myeloid leukemia.
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Muratoğlu Bihter, Özdemir Cansu, Eylem Cemil Can, Reçber Tuba, Nemutlu Emirhan, Uçkan-Çetinkaya Duygu
Аннотация
BACKGROUND: The circadian rhythms, intrinsic 24-hour oscillations in physiological and cellular processes, serve as fundamental regulators of cellular function and metabolism. Although these rhythms are robust, they are susceptible to dysregulation, particularly in hematological diseases, where circadian misalignment exacerbates pathological conditions. The role of bone marrow adipose tissue mesenchymal stem cells (BMAT-MSCs), a dynamic component of the bone marrow microenvironment, in the pathogenesis of Fanconi anemia (FA), a genetic disorder characterized by a predisposition to myeloproliferative disease and acute myeloid leukemia (AML), remains poorly understood. This study explores the potential therapeutic applications of dexamethasone (DEX)-induced synchronization in BMAT-MSCs derived from healthy donors (HD), FA, and AML.
METHODS AND RESULTS: BMAT-MSCs were subjected to DEX-induced synchronization to emulate in vivo conditions, after which comprehensive analyses of circadian gene expression, metabolomic and lipidomic profiles were conducted. Synchronization restored PER1 rhythmicity across all groups, indicating effective circadian entrainment, whereas CRY1 rhythms were attenuated in FA and AML. Lipidomic and metabolomic readouts under synchronized conditions showed more consistent, timepoint-aligned patterns than in unsynchronized cells, enabling clearer identification of group-specific alterations, including changes related to phospholipid/lipid remodeling pathways.
CONCLUSIONS: These data indicate that circadian synchronization improves interpretability of BMAT-MSC molecular outputs and reveals disease-associated differences among HD, FA, and AML. This study is a preliminary investigation with limited sampling and timepoints; findings should be validated in larger cohorts with denser temporal resolution. Overall, the results provide a framework for integrating circadian context into BMAT-MSC analyses in health and hematological disease.
METHODS AND RESULTS: BMAT-MSCs were subjected to DEX-induced synchronization to emulate in vivo conditions, after which comprehensive analyses of circadian gene expression, metabolomic and lipidomic profiles were conducted. Synchronization restored PER1 rhythmicity across all groups, indicating effective circadian entrainment, whereas CRY1 rhythms were attenuated in FA and AML. Lipidomic and metabolomic readouts under synchronized conditions showed more consistent, timepoint-aligned patterns than in unsynchronized cells, enabling clearer identification of group-specific alterations, including changes related to phospholipid/lipid remodeling pathways.
CONCLUSIONS: These data indicate that circadian synchronization improves interpretability of BMAT-MSC molecular outputs and reveals disease-associated differences among HD, FA, and AML. This study is a preliminary investigation with limited sampling and timepoints; findings should be validated in larger cohorts with denser temporal resolution. Overall, the results provide a framework for integrating circadian context into BMAT-MSC analyses in health and hematological disease.