Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Overlapping and distinct roles of LIN28 paralogs in reprogramming and stem cell metabolism

ABSTRACT: The RNA binding protein paralogs LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency. Somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by overexpression of OCT4 and SOX2 together with NANOG and LIN28A (OSNA), but the exact roles LIN28A/B play are still poorly understood. Here we show that LIN28B likewise promotes reprogramming, and that reactivation of both endogenous LIN28A and B loci are required for maximal reprogramming efficiency. The LIN28B locus has open chromatin and is activated early during reprogramming, whereas LIN28A is activated at later stages by OCT4, marking the transition to bona fide iPS cells. By proteomic and metabolomic analysis, we demonstrate that LIN28A chiefly regulates let-7 and protein translation, whereas LIN28B promotes embryonic metabolism by repressing oxidative phosphorylation and enhancing glycolysis. Thus, LIN28A and LIN28B play independent and cooperative roles in reprogramming and pluripotent stem cell metabolism. 8 samples in total were analyzed. 2 replicates for each phenotypes. Controls are the wild type (flox) without lin28a/b loss of function.

ORGANISM(S): Mus musculus

SUBMITTER: JIN ZHANG

PROVIDER: E-GEOD-66838 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Background: MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functional role of miRNAs in murine models of colitis facilitates elucidating the role of specific miRNAs in human IBD. The aim of this study was to determine the miRNA signature of murine models of colitis and to assess the influence of miR-21 on intestinal inflammation. Methods: miRNAs expression was accessed by microarray for acute and chronic murine model of colitis induced by DSS or TNBS. miR-21-deficient mouse and littermates controls were assessed in the standard DSS, TNBS and CD4+ T cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RBHigh cells were analyzed by miRNA and mRNA microarray, and quantitative RT-PCR. Th1 polarization was accessed by flow-cytometry and ELISA. Results: Alterations of in miRNAs expression were identified for acute and chronic DSS colitis and TNBS colitis, receptively. The Expression of miRs-21, -142-3p and -223 was were distinct between DSS and TNBS models while overlap of numerous miRNAs was seen. Importantly, miRs-19b, -192 and -215, that are decreased in IBD, were significantly decreased in all 4 models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis but not the DSS colitis models. Further assessment of the miR-21-deficient 1-/- mice revealed that the deletion of miR-21 results in the exacerbation of both the TNBS and T cell-transfer models of colitis. Conclusions: miRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21 deletion exacerbated CD4+ T cell-mediated models of colitis provides further evidence that miRNAs play significant roles in the pathogenesis of IBD. Gene expression profiles were established for normal miR-21-/- mice and wild type c57BL/6 mice (WT). Total of 6 samples with replicates were included in this study.

Dataset Information

Overlapping and distinct roles of LIN28 paralogs in reprogramming and stem cell metabolism

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure