MULTİ-OMİKS YAKLAŞIMI İLE KEMİK İLİĞİ YAĞ-SPESİFİK ARİLHİDROKARBON RESEPTÖRÜNÜN (AHR) SİRKADİYEN SAAT REGÜLASYONUNDAKİ ROLÜNÜN İNCELENMESİ

Abstract

Bone marrow (BM) is a complex microenvironment consisting of various cell types, and bone marrow adipose tissue (BMAT) within this structure is a dynamic component that regulates tissue functions and disease pathogenesis. Lipolysis in BMAT supports the survival of leukemic cells, but its primary role in leukemia development remains insufficiently understood. Fanconi anemia (FA), characterized by susceptibility to acute myeloid leukemia (AML) and sensitivity to environmental toxins, serves as a suitable transitional model for studying leukemic transformation. Circadian rhythms, which exhibit intrinsic 24-hour oscillations, are robust but prone to dysfunction, exacerbating pathological conditions in hematological diseases. This study compared the differentiation potentials and secretory profiles of BM-mesenchymal stem cells (BM-MSCs) and BMATMSCs isolated from donors, FA, and AML patients. Following the characterization study, molecular analyses were performed on synchronized and unsynchronized BMAT-MSCs, demonstrating that circadian synchronization plays a crucial role in aligning cellular functions in healthy and pathological conditions. Under SR1 exposure, an AhR antagonist, transcriptomic, metabolomic, and lipidomic analyses were conducted on BMAT-MSCs. The multi-omics approach provided a holistic assessment of the interactions between genes, metabolites, and lipids. As a result, the interactions between AhR signaling and circadian rhythms revealed the potential role of BMAT-MSCs in leukemia pathogenesis and offered strategic approaches for circadian rhythm-based therapies and transcriptomic and metabolic targets.