Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression.

DNA methylation is crucial for chromatin structure, transcription regulation and genome stability, defining cellular identity. Aberrant hypermethylation of CpG-rich regions is common in cancer, influencing gene expression. However, the specific contributions of individual epigenetic modifications to tumorigenesis remain under investigation.

M1BP is an essential transcriptional activator of oxidative metabolism during Drosophila development.

Oxidative metabolism is the predominant energy source for aerobic muscle contraction in adult animals. How the cellular and molecular components that support aerobic muscle physiology are put in place during development through their transcriptional regulation is not well understood. Using the Drosophila flight muscle model, we show that the formation of mitochondria cristae harbouring the respiratory chain is concomitant with a large-scale transcriptional upregulation of genes linked with oxidative phosphorylation (OXPHOS) during specific stages of flight muscle development.

A live-imaging protocol to track cell movement in the embryo.

Tracking individual cell movement during development is challenging, particularly in tissues subjected to major remodeling. Currently, most live imaging techniques in are limited to tissue explants and/or to superficial cells. We describe here a protocol to track immature multiciliated cells (MCCs) moving within the inner epidermal layer of a whole embryo.

Endogenous neural stem cells modulate microglia and protect against demyelination.

In response to corpus callosum (CC) demyelination, subventricular zone-derived neural progenitors (SVZdNPs) are mobilized and generate new myelinating oligodendrocytes (OLG). Here, we examine the putative immunomodulatory properties of endogenous SVZdNPs during demyelination in the cuprizone model. SVZdNP density was higher in the lateral and rostral CC regions, and demyelination was inversely correlated with activated microglial density and pro-inflammatory cytokine levels.

Myofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle.

Complex animals build specialised muscles to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres and mitochondria are muscle type specific. However, mechanisms coordinating mitochondria with sarcomere morphogenesis are elusive.

The Scf/Kit pathway implements self-organized epithelial patterning.

How global patterns emerge from individual cell behaviors is poorly understood. In the Xenopus embryonic epidermis, multiciliated cells (MCCs) are born in a random pattern within an inner mesenchymal layer and subsequently intercalate at regular intervals into an outer epithelial layer. Using video microscopy and mathematical modeling, we found that regular pattern emergence involves mutual repulsion among motile immature MCCs and affinity toward outer-layer intercellular junctions.

Modeling Heterogeneity of Triple-Negative Breast Cancer Uncovers a Novel Combinatorial Treatment Overcoming Primary Drug Resistance.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype characterized by a remarkable molecular heterogeneity. Currently, there are no effective druggable targets and advanced preclinical models of the human disease. Here, a unique mouse model ( mice) of mammary tumors driven by a subtle increase in the expression of the wild-type MET receptor is generated.

ADAMTSL5 is an epigenetically activated gene underlying tumorigenesis and drug resistance in hepatocellular carcinoma.

Background & Aims: The tumour microenvironment shapes tumour growth through cellular communications that include both direct interactions and secreted factors. The aim of this study was to characterize the impact of the secreted glycoprotein ADAMTSL5, whose role in cancer has not been previously investigated, on hepatocellular carcinoma (HCC).

Methods: ADAMTSL5 methylation status was evaluated through bisulfite sequencing, and publicly available data analysis.

Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in neuroblast tumors.

It is still unclear what drives progression of childhood tumors. During larval development, asymmetrically-dividing neural stem cells, called neuroblasts, progress through an intrinsic temporal patterning program that ensures cessation of divisions before adulthood. We previously showed that temporal patterning also delineates an early developmental window during which neuroblasts are susceptible to tumor initiation (Narbonne-Reveau et al.

Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis.

Background & Aims: The variety of alterations found in hepatocellular carcinoma (HCC) makes the identification of functionally relevant genes and their combinatorial actions in tumorigenesis challenging. Deregulation of receptor tyrosine kinases (RTKs) is frequent in HCC, yet little is known about the molecular events that cooperate with RTKs and whether these cooperative events play an active role at the root of liver tumorigenesis.

Methods: A forward genetic screen was performed using Sleeping Beauty transposon insertional mutagenesis to accelerate liver tumour formation in a genetic context in which subtly increased MET RTK levels predispose mice to tumorigenesis.

Publisher Correction: Hypermethylation of gene body CpG islands predicts high dosage of functional oncogenes in liver cancer.

In the original version of this Article, the sixth sentence of the abstract incorrectly read 'Most of the genes upregulated and with hypermethylated CGIs in the Alb-R26Met HCC model undergo the same change.', and should have read 'Most of the genes upregulated and with hypermethylated CGIs in the Alb-R26Met HCC model undergo the same change in a large proportion of HCC patients.'.

Hypermethylation of gene body CpG islands predicts high dosage of functional oncogenes in liver cancer.

Epigenetic modifications such as aberrant DNA methylation reshape the gene expression repertoire in cancer. Here, we used a clinically relevant hepatocellular carcinoma (HCC) mouse model (Alb-R26) to explore the impact of DNA methylation on transcriptional switches associated with tumorigenesis. We identified a striking enrichment in genes simultaneously hypermethylated in CpG islands (CGIs) and overexpressed.

A pipeline for the systematic identification of non-redundant full-ORF cDNAs for polymorphic and evolutionary divergent genomes: Application to the ascidian Ciona intestinalis.

Genome-wide resources, such as collections of cDNA clones encoding for complete proteins (full-ORF clones), are crucial tools for studying the evolution of gene function and genetic interactions. Non-model organisms, in particular marine organisms, provide a rich source of functional diversity. Marine organism genomes are, however, frequently highly polymorphic and encode proteins that diverge significantly from those of well-annotated model genomes.

Rapid evolutionary responses of life history traits to different experimentally-induced pollutions in Caenorhabditis elegans.

Background: Anthropogenic disturbances can lead to intense selection pressures on traits and very rapid evolutionary changes. Evolutionary responses to environmental changes, in turn, reflect changes in the genetic structure of the traits, accompanied by a reduction of evolutionary potential of the populations under selection. Assessing the effects of pollutants on the evolutionary responses and on the genetic structure of populations is thus important to understanding the mechanisms that entail specialization to novel environmental conditions or resistance to novel stressors.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures.

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies.

Creating 3D digital replicas of ascidian embryos from stacks of confocal images.

During embryonic development, cell behaviors that are tightly coordinated both spatially and temporally integrate at the tissue level and drive embryonic morphogenesis. Over the past 20 years, advances in imaging techniques, in particular, the development of confocal imaging, have opened a new world in biology, not only giving us access to a wealth of information, but also creating new challenges. It is sometimes difficult to make the best use of the recordings of the complex, inherently three-dimensional (3D) processes we now can observe.

Imaging of fixed ciona embryos for creating 3D digital replicas.

During embryonic development, cell behaviors that are tightly coordinated both spatially and temporally integrate at the tissue level and drive embryonic morphogenesis. Over the past 20 years, advances in imaging techniques, in particular, the development of confocal imaging, have opened a new world in biology, not only giving us access to a wealth of information, but also creating new challenges. It is sometimes difficult to make the best use of the recordings of the complex, inherently three-dimensional (3D) processes we now can observe.

Time-lapse imaging of live Phallusia embryos for creating 3D digital replicas.

During embryonic development, cell behaviors that are tightly coordinated both spatially and temporally integrate at the tissue level and drive embryonic morphogenesis. Over the past 20 years, advances in imaging techniques, in particular, the development of confocal imaging, have opened a new world in biology, not only giving us access to a wealth of information, but also creating new challenges. It is sometimes difficult to make the best use of the recordings of the complex, inherently three-dimensional (3D) processes we now can observe.

The ANISEED database: digital representation, formalization, and elucidation of a chordate developmental program.

Developmental biology aims to understand how the dynamics of embryonic shapes and organ functions are encoded in linear DNA molecules. Thanks to recent progress in genomics and imaging technologies, systemic approaches are now used in parallel with small-scale studies to establish links between genomic information and phenotypes, often described at the subcellular level. Current model organism databases, however, do not integrate heterogeneous data sets at different scales into a global view of the developmental program.

A cis-regulatory signature in ascidians and flies, independent of transcription factor binding sites.

Background: Transcription initiation is controlled by cis-regulatory modules. Although these modules are usually made of clusters of short transcription factor binding sites, a small minority of such clusters in the genome have cis-regulatory activity. This paradox is currently unsolved.

Minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE).

One purpose of the biomedical literature is to report results in sufficient detail that the methods of data collection and analysis can be independently replicated and verified. Here we present reporting guidelines for gene expression localization experiments: the minimum information specification for in situ hybridization and immunohistochemistry experiments (MISFISHIE). MISFISHIE is modeled after the Minimum Information About a Microarray Experiment (MIAME) specification for microarray experiments.

A quantitative approach to the study of cell shapes and interactions during early chordate embryogenesis.

Background: The prospects of deciphering the genetic program underlying embryonic development were recently boosted by the generation of large sets of precisely organized quantitative molecular data. In contrast, although the precise arrangement, interactions, and shapes of cells are crucial for the fulfilment of this program, their description remains coarse and qualitative. To bridge this gap, we developed a generic software, 3D Virtual Embryo, to quantify the geometry and interactions of cells in interactive three-dimensional embryo models.