Present evidence suggests that E2F2 may act both as a suppressor and promoter of proliferation, depending on the cellular context. We used a loss-of-function mutant mouse model to investigate the function of E2F2 in liver regeneration after partial hepatectomy, a paradigm of cell-cycle progression. Liver mass recovery and histology were examined over 9 days in 70% hepatectomized E2F2Ϫ/Ϫ and wild-type animals. Transcriptome analysis was performed in quiescent and 48-h regenerating liver samples. TIGR MultiExperiment Viewer was used for the statistical analysis of microarray data, significance was determined by Fischer, and P values were adjusted applying BenjaminiHochberg multiple-testing correction. We show that E2F2 is required for adult hepatocyte proliferation and for timely liver regeneration, as disruption of the E2F2 gene in hepatocytes leads to a reduced rate of S-phase entry and to delayed liver regeneration. Transcriptome analysis followed by ontological classification of differentially expressed genes and gene-interaction network analysis indicated that the majority of genes involved in normal liver regeneration were related to biosynthetic and catabolic processes of all major biomolecules as well as cellular location and intracellular transport, confirming the complex nature of the regeneration process. Remarkably, transcripts of genes included in functional categories that are crucial for cell cycle, apoptosis and wound-healing response, and fibrosis were absent in the transcriptome of posthepatectomized E2F2 Ϫ/Ϫ mice. Our results indicate that the transcriptional activity of E2F2 contributes to promote adult hepatocyte proliferation and liver regeneration. cell cycle; transcriptome; liver repair; partial hepatectomy THE E2F TRANSCRIPTION FACTORS are key regulators of cell proliferation and rate-limiting factors in the S-phase entry, as they regulate the expression of many genes involved in the G 1 /S transition. According to the most accepted model of cell-cycle control, unphosphorylated retinoblastoma tumor suppressor protein (pRb) binds to E2F in G 0 /G 1 , forming a complex that actively represses E2F-responsive genes. In late G 1 pRb is inactivated because of phosphorylation by cyclin-dependent kinases, releasing free E2Fs that activate the expression of their target genes (4,12,42).The E2F family is presently composed of nine members encoded by eight different genes (E2F1-8) (4,12,20,42).Members of E2F family can be classified into "activators" (E2F1-3a) and "repressors" (E2F3b-8). Activator E2Fs are considered potent activators of transcription and positive regulators of the cell cycle. Overexpression of any of these activator E2Fs is sufficient to promote G 1 /S transition and DNA replication in immortalized, quiescent rodent fibroblasts in the absence of growth factors (23). However, there is increasing evidence that they may also act as transcriptional repressors (2,7,18,28). E2F1 seems to act both as an oncogene and as a tumor suppressor in the liver (6) but was found not to be essential f...

For many years, traditional histology has been the gold standard for the diagnosis of many diseases. However, alternative and powerful techniques have appeared in recent years that complement the information extracted from a tissue section. One of the most promising techniques is imaging mass spectrometry applied to lipidomics. Here, we demonstrate the capabilities of this technique to highlight the architectural features of the human kidney at a spatial resolution of 10 μm. Our data demonstrate that up to seven different segments of the nephron and the interstitial tissue can be readily identified in the sections according to their characteristic lipid fingerprints and that such fingerprints are maintained among different individuals ( n = 32). These results set the foundation for further studies on the metabolic bases of the diseases affecting the human kidney.

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The mammalian liver, a key organ in lipid homeostasis, can accumulate increased amounts of lipids in certain physiological conditions including liver regeneration. Lipid droplets (LD), the lipid storage organelles in the cytoplasm, are composed of a core of neutral lipids (mainly triacylglycerols and cholesteryl esters) surrounded by a monolayer of phospholipids and cholesterol with associated proteins. It is recognized that LD lipid composition is cell- and environment-specific and enables LD to carry out specific functions, but few descriptive studies aiming to interpret such differences have been published. We characterized eight density fractions of LD isolated from quiescent (control) and regenerating liver after partial hepatectomy, and grouped populations according to their lipid composition. LD from quiescent liver resembled the cholesteryl ester storage LD found in steroidogenic tissues, whereas in the regenerating tissue they were similar to adipocyte LD. Specifically, there were large, light LD with increased triacylglycerol content, the hallmark of liver regeneration. The apparent volume of the dense LD was, however, lower than in the quiescent density-matched populations, concomitant with increased phosphatidylcholine and phosphatidylethanolamine and decreased neutral lipid content. Analysis of the lipid profile of LD populations from quiescent and regenerating tissue leads us to define four physiological LD phenotypes for rat liver.