Iogenic agents. In addition, 0 cells play a critical role in the
Iogenic agents. In addition, 0 cells play a critical role in the production of cybrid (cytoplasmic hybrid) cell lines containing specific mutations in mtDNA. While multiple groups have used this elegant system to study mitochondrial function in cultured cells (see reviews [4,75]), only recently have these cybrids been used in tumor xenografts [64]. Gene expression profiling of such cybrids both in culture and in xenografts could provide valuable data to elucidate further the functional interactions between the nuclear and mitochondrial genomes.ConclusionAlthough growth conditions had a greater influence on gene expression profiles than the presence of active mitochondria, we identified mtDNA-dependent gene expression profiles that are shared in cultured A549 cells and in xenografts. These profiles indicate that cells with mtDNA alterations have distinct biochemical properties that make them well-suited for elucidating responses to physiological perturbations, such as changes in oxygen and glucose levels, and testing the effects of specialized classes of chemotherapeutic agents. In addition, our studies suggest that gene expression profiling of mtDNA-depleted cells grown culture and in xenografts provide powerful means to investigate possible relationships between mitochondrial activity and gene expression profiles in normal and pathological cells.Authors’ contributionsJP carried out flow cytometry and immunoassays. PT and XM performed the xenograft studies. PL prepared mtDNAdepleted cells, performed oxygen consumption, flow cytometry, and ELISA assays, and participated in the design of the study. PKD performed gene expression profiling experiments and assisted in data analysis. KR performed mtDNA quantification studies. DMT and KDS analyzed gene expression data. DM and JH conceived of the study, interpreted the data, and wrote the manuscript.Additional material Additional fileAnalysis of mitochondrial-encoded RNA transcript levels in A549 and A549 0 xenografts by quantitative RT-PCR. Mitochondrial-encoded RNA transcript levels in A549 and A549 0 xenografts are quantified by RT-PCR. Click here for file [http://www.ZM241385 web biomedcentral.com/content/supplementary/14712164-9-521-S1.ppt]Page 16 of(page number not for citation purposes)BMC Genomics 2008, 9:http://www.biomedcentral.com/1471-2164/9/Additional fileProcessed gene expression scores for all microarray analyses. Gene expression scores for all microarray experiments described in this manuscript. Click here for file [http://www.biomedcentral.com/content/supplementary/14712164-9-521-S2.xls]Additional fileDifferential expression in A549 xenografts and A549 cell cultures. Probe sets showing differential expression in A549 xenografts and A549 cell cultures are provided. Click here for file [http://www.biomedcentral.com/content/supplementary/14712164-9-521-S9.xls]Additional fileVolcano plots for gene expression comparisons considered in this study. The relationships between fold changes and P-values for the gene expression comparisons made in this study are provided. Click here for file [http://www.biomedcentral.com/content/supplementary/14712164-9-521-S3.ppt]Differential expression in A549 0 xenografts and A549 0 cell cultures. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25962748 Probe sets showing differential expression in A549 0xenografts and A549 0 cell cultures are provided. Click here for file [http://www.biomedcentral.com/content/supplementary/14712164-9-521-S10.xls]Additional fileDifferentially expressed transcripts in A549 0 and A549 cells.
