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MiRNA expression profile in mouse CD34+/CD105- cells derived from the renal artery subsequent to renal ischemia/reperfusion injury

ABSTRACT: MiRNA regulate the maintenance, differentiation and function of stem cells and progenitor cells. miRNA expression of progenitor cells located in the adventital layer of arterial vessels has not been characterized in either animal or human models. Further it is unknown if local arterial miRNA expression profiles change after injury of end organs supplied blood by these arterial conduits. CD34+/CD105- cells were extracted and analyzed for changes in miRNA expression after kidney specific ischemic injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE68367 | GEO | 2015/04/29

SECONDARY ACCESSION(S): PRJNA282525

REPOSITORIES: GEO

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Project description:Recent advancement in cancer research has shown that tumours are highly heterogeneous and multiple phenotypically different cell populations are found in single nodule. Cancer development and tumour growth is driven by specific type of cells - cancer stem cells or tumour initiating cells (CSCs/TICs), which are to be responsible for tumour growth, metastatic spread and drug resistance. This research was designed to verify the presence of tumour initiating cells in renal cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumour initiating cells. Main goal of the project was to describe gene expression profile of tumour initiating cells originating from primary tumour and of metastatic origin. Metastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony forming ability comparing to primary RCC cell lines. We investigated presence of CD105+ cells in RCC cell lines. Furthermore, metastatic RCC cell lines have higher CD105+ cell population and higher expression for stemness genes (Oct-4 and Nanog). CD105+ cells adopt 3D grapes like structure under handing drop condition. Sorted CD105+ cells were found positive for human MSC makers such as CD90, CD73, CD44, CD146 and alkaline phosphatase activity. In addition, CD105+ cells were unable to expressed maker for CD24, CD34, CD11b, CD19, CD45 and HLA-DR. 1411 genes were commonly differentially expressed in CD105+ cells (both from primary (Caki-2) and metastatic RCC (ACHN)) cells in comparison to healthy kidney epithelial cell line (ASE-5063). TGF-β, Wnt/β-catenine, Epithelial-Mesenchymal Transition (EMT), Rap1 signaling, PI3K-Akt signaling and Hippo signaling pathway were altered in CD105+ cells after IPA and KEGG pathway analysis. TGFB1, ERBB2, and TNF are most significant transcriptional regulators activated in these cells. Altogether, our results indicate that RCC-CD105+ cells may represents a novel target for CSCs/TICs phenotype and their gene expression profile could be used as initial data for new functional studies and drug design.

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MiRNA expression profile in mouse CD34+/CD105- cells derived from the renal artery subsequent to renal ischemia/reperfusion injury

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