Metabolom ve Transkriptom Profillemesi ile İnsan Kemik İliğinde Hematopoetik Niş Karakterizasyonu

Abstract

In model organisms and animal experiments, it has been shown that hematopoietic stem cells (HSC) in bone marrow have special organizations and they provide this organization through special microenvironment called niche. According to these studies, it is known that in HSC niche there are two different niches including endosteal and vascular niche. This study is conducted to investigate and characterization of presence of different niches in the bone marrow of healthy people, it carries the first of its kind in this area. In this study, the presence of niches in healthy human bone marrow was investigated using omics technologies: transcriptomics using the RNA-Seq technique and metabolomics using GC-MS technique. For this purpose, in this study it has been made comparative analysis with niche characterization, isolating plasma and mesenchymal stem cells from bone marrow samples taken from two different bone marrow areas (endosteal area=Niche1 and vascular niche=Niche2) of healthy donors. 54 differentially expressed genes were identified as a result of Niche1 and Niche2 comparative RNA-Seq analysis (p<0,05). It was determined different levels of metabolites associated with energy metabolisms and sphingosine metabolism in Niche1 and Niche2 with GC-MS analysis (p<0,05).Our results so far as we know theoretically support the information that undifferentiated HSCs in the bone marrow remain silent without differentiation in endosteal area (Niche1) known as hypoxic but when there is a stimulus mediated stress or neurotransmitters they migrated to the vascular area (Niche2). These findings are also confirmed feasibility of specimen handling technique from different bone marrow niches that we use for the first time in our study. In this study, theoretical hypotheses on the presence of different niche in the human bone marrow was tested using omiks technologies and molecular markers belong to these niche have been identified for the first time so it will be a reference to the literature. Key words: Bone marrow, Niche, Transcriptome, Metabolome