References of "Fouquier d'Hérouël, Aymeric 50001802"
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See detailMutations in RHOT1 disrupt ER-mitochondria contact sites interfering with calcium homeostasis and mitochondrial dynamics in Parkinson's disease.
Grossmann, Dajana UL; Berenguer, Clara UL; Bellet, Marie Estelle et al

in Antioxidants & redox signaling (2019)

OBJECTIVE: The outer mitochondrial membrane protein Miro1 is a crucial player in mitochondrial dynamics and calcium homeostasis. Recent evidence indicated that Miro1 mediates calcium-induced mitochondrial ... [more ▼]

OBJECTIVE: The outer mitochondrial membrane protein Miro1 is a crucial player in mitochondrial dynamics and calcium homeostasis. Recent evidence indicated that Miro1 mediates calcium-induced mitochondrial shape transition (MiST), which is a prerequisite for the initiation of mitophagy. Moreover, altered Miro1 protein levels have emerged as a shared feature of monogenic and sporadic Parkinson's disease (PD), but, so far, no disease-associated variants in RHOT1 have been identified. RESULTS: Here, for the first time, we describe heterozygous RHOT1 mutations in two PD patients (het c.815G>A; het c.1348C>T) and identified mitochondrial phenotypes with reduced mitochondrial mass in patient-derived cellular models. Both mutations lead to decreased ER-mitochondrial contact sites and calcium dyshomeostasis. As a consequence, energy metabolism was impaired, which in turn lead to increased mitophagy. CONCLUSION: In summary, our data support the role of Miro1 in maintaining calcium homeostasis and mitochondrial quality control in PD. [less ▲]

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See detailA Specialized Method to Resolve Fine 3D Features of Astrocytes in Nonhuman Primate (Marmoset, Callithrix jacchus) and Human Fixed Brain Samples.
Quesseveur, Gael; Fouquier d'Hérouël, Aymeric UL; Murai, Keith K. et al

in Methods in molecular biology (Clifton, N.J.) (2019), 1938

Astrocytes are among the most numerous cells in the brain and fulfill diverse functions in homeostasis and regulation of neuronal activity. Astrocytes also dramatically change their properties in response ... [more ▼]

Astrocytes are among the most numerous cells in the brain and fulfill diverse functions in homeostasis and regulation of neuronal activity. Astrocytes also dramatically change their properties in response to brain injury or disease, a process called reactive gliosis. Precisely how astrocytes contribute to healthy brain function and play differential roles in brain pathology and regeneration remain important areas of investigation. To better understand the properties of astrocytes, more sophisticated approaches for probing their rich and complex anatomical and molecular features are needed to fully determine their contribution to brain physiology. Here we present an efficient and straightforward immunolabeling protocol to obtain high-resolution fluorescence-based images from fixed nonhuman primate (common marmoset Callithrix jacchus) and human brain samples. Importantly, the protocol is useful for obtaining images from samples that have been stored in fixative solutions (such as formalin) for years. This approach is especially useful for three-dimensional, multichannel confocal microscopy and can be optimized for super-resolution techniques such as stimulated emission depletion (STED) microscopy. We also present a strategy for using specific combinations of markers to define the phenotypic variations and cellular/subcellular properties of astrocytes to better predict the function of these cells on their surrounding brain microenvironment. [less ▲]

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See detailAn observation of circular RNAs in bacterial RNA-seq data
Innocenti, Nicolas; Nguyen, Hoang-Son; Fouquier d'Hérouël, Aymeric UL et al

E-print/Working paper (2016)

Circular RNAs (circRNAs) are a class of RNA with an important role in micro RNA (miRNA) regulation recently discovered in Human and various other eukaryotes as well as in archaea. Here, we have analyzed ... [more ▼]

Circular RNAs (circRNAs) are a class of RNA with an important role in micro RNA (miRNA) regulation recently discovered in Human and various other eukaryotes as well as in archaea. Here, we have analyzed RNA-seq data obtained from Enterococcus faecalis and Escherichia coli in a way similar to previous studies performed on eukaryotes. We report observations of circRNAs in RNA-seq data that are reproducible across multiple experiments performed with different protocols or growth conditions. [less ▲]

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See detailLoss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism
Meiser, Johannes UL; Delcambre, Sylvie UL; Wegner, André UL et al

in Neurobiology of disease (2016), 89

The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an ... [more ▼]

The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro-inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches. [less ▲]

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See detailRelative Stability of Network States in Boolean Network Models of Gene Regulation in Development
Zhou, Joseph Xu; Samal, Areejit; Fouquier d'Hérouël, Aymeric UL et al

in Biosystems (2016), 142

Progress in cell type reprogramming has revived the interest in Waddington’s concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington’s ... [more ▼]

Progress in cell type reprogramming has revived the interest in Waddington’s concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington’s landscape. The Quasi-potential U(x), derived from interactions in the gene regulatory network (GRN) of a cell, quantifies the relative stability of network states, which determine the effort required for state transitions in a multi-stable dynamical system. However, quasi-potential landscapes, originally developed for continuous systems, are not suitable for discrete-valued networks which are important tools to study complex systems. In this paper, we provide a framework to quantify the landscape for discrete Boolean networks (BNs). We apply our framework to study pancreas cell differentiation where an ensemble of BN models is considered based on the structure of a minimal GRN for pancreas development. We impose biologically motivated structural constraints (corresponding to specific type of Boolean functions) and dynamical constraints (corresponding to stable attractor states) to limit the space of BN models for pancreas development. In addition, we enforce a novel functional constraint corresponding to the relative ordering of attractor states in BN models to restrict the space of BN models to the biological relevant class. We find that BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics of pancreas cell differentiation. This framework can also determine the genes' influence on cell state transitions, and thus can facilitate the rational design of cell reprogramming protocols. [less ▲]

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See detailConceptual Confusion: the case of Epigenetics
Oliveira Pisco, Angela; Fouquier d'Hérouël, Aymeric UL; Huang, Sui

E-print/Working paper (2016)

The observations of phenotypic plasticity have stimulated the revival of "epigenetics". Over the past 70 years the term has come in many colors and flavors, depending on the biological discipline and time ... [more ▼]

The observations of phenotypic plasticity have stimulated the revival of "epigenetics". Over the past 70 years the term has come in many colors and flavors, depending on the biological discipline and time period. The meanings span from Waddington "epigenotype" and "epigenetic landscape" to the molecular biologists "epigenetic marks" embodied by DNA methylation and histone modifications. Here we seek to quell the ambiguity of the name. First we place "epigenetic" in the various historical contexts. Then, by presenting the formal concepts of dynamical systems theory we show that the "epigenetic landscape" is more than a metaphor: it has specific mathematical foundations. The latter explains how gene regulatory networks produce multiple attractor states, the self-stabilizing patterns of gene activation across the genome that account for "epigenetic memory". This network dynamics approach replaces the reductionist correspondence of molecular epigenetic modifications with concept of the epigenetic landscape, by providing a concrete and crisp correspondence. [less ▲]

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See detailStemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival.
Grosse-Wilde, Anne; Fouquier d'Hérouël, Aymeric UL; McIntosh, Ellie et al

in PLoS ONE (2015), 10(5), 0126522

Breast cancer stem cells (CSCs) are thought to drive recurrence and metastasis. Their identity has been linked to the epithelial to mesenchymal transition (EMT) but remains highly controversial since ... [more ▼]

Breast cancer stem cells (CSCs) are thought to drive recurrence and metastasis. Their identity has been linked to the epithelial to mesenchymal transition (EMT) but remains highly controversial since-depending on the cell-line studied-either epithelial (E) or mesenchymal (M) markers, alone or together have been associated with stemness. Using distinct transcript expression signatures characterizing the three different E, M and hybrid E/M cell-types, our data support a novel model that links a mixed EM signature with stemness in 1) individual cells, 2) luminal and basal cell lines, 3) in vivo xenograft mouse models, and 4) in all breast cancer subtypes. In particular, we found that co-expression of E and M signatures was associated with poorest outcome in luminal and basal breast cancer patients as well as with enrichment for stem-like cells in both E and M breast cell-lines. This link between a mixed EM expression signature and stemness was explained by two findings: first, mixed cultures of E and M cells showed increased cooperation in mammosphere formation (indicative of stemness) compared to the more differentiated E and M cell-types. Second, single-cell qPCR analysis revealed that E and M genes could be co-expressed in the same cell. These hybrid E/M cells were generated by both E or M cells and had a combination of several stem-like traits since they displayed increased plasticity, self-renewal, mammosphere formation, and produced ALDH1+ progenies, while more differentiated M cells showed less plasticity and E cells showed less self-renewal. Thus, the hybrid E/M state reflecting stemness and its promotion by E-M cooperation offers a dual biological rationale for the robust association of the mixed EM signature with poor prognosis, independent of cellular origin. Together, our model explains previous paradoxical findings that breast CSCs appear to be M in luminal cell-lines but E in basal breast cancer cell-lines. Our results suggest that targeting E/M heterogeneity by eliminating hybrid E/M cells and cooperation between E and M cell-types could improve breast cancer patient survival independent of breast cancer-subtype. [less ▲]

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See detailWhole genome mapping of 5' ends in bacteria by tagged sequencing: A comprehensive view in Enterococcus faecalis
Innocenti, Nicolas; Golumbeanu, Monica; Fouquier d'Hérouël, Aymeric UL et al

in RNA (New York, N.Y.) (2015), 21(5), 1018-1030

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See detailRegulatory crosstalk between type I and type II toxin-antitoxin systems in the human pathogen Enterococcus faecalis.
Wessner, Francoise; Lacoux, Caroline; Goeders, Nathalie et al

in RNA biology (2015), 12(10), 1099-1108

We discovered a chromosomal locus containing two toxin-antitoxin modules (TAs) with an antisense transcriptional organization in the E. faecalis clinical isolate V583. These TAs are homologous to the type ... [more ▼]

We discovered a chromosomal locus containing two toxin-antitoxin modules (TAs) with an antisense transcriptional organization in the E. faecalis clinical isolate V583. These TAs are homologous to the type I txpA-ratA system and the type II mazEF, respectively. We have shown that the putative MazF is toxic for E. coli and triggers RNA degradation, and its cognate antitoxin MazE counteracts toxicity. The second module, adjacent to mazEF, expresses a toxin predicted to belong to the TxpA type I family found in Firmicutes, and the antisense RNA antidote, RatA. Genomic analysis indicates that the cis-association of mazEF and txpA-ratA modules has been favored during evolution, suggesting a selective advantage for this TA organization in the E. faecalis species. We showed regulatory interplays between the two modules, involving transcription control and RNA stability. Remarkably, our data reveal that MazE and MazEF have a dual transcriptional activity: they act as autorepressors and activate ratA transcription, most likely in a direct manner. RatA controls txpA RNA levels through stability. Our data suggest a pivotal role of MazEF in the coordinated expression of mazEF and txpA-ratA modules in V583. To our knowledge, this is the first report describing a crosstalk between type I and II TAs. [less ▲]

Detailed reference viewed: 77 (3 UL)
See detailDiscrete Gene Network Models for Understanding Multicellularity and Cell Reprogramming: From Network Structure to Attractor Landscape
Zhou, Joseph Xu; Qiu, Xiaojie; Fouquier d'Hérouël, Aymeric UL et al

in Eils, Roland; Kriete, Andreas (Eds.) Computational Systems Biology (2014)

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See detailDirect elicitation of template concentration from quantification cycle (Cq) distributions in digital PCR
Mojtahedi, Mitra; Fouquier d'Hérouël, Aymeric UL; Huang, Sui

in Nucleic Acids Research (2014), 42(16), 126

Digital PCR (dPCR) exploits limiting dilution of a template into an array of PCR reactions. From this array the number of reactions that contain at least one (as opposed to zero) initial template is ... [more ▼]

Digital PCR (dPCR) exploits limiting dilution of a template into an array of PCR reactions. From this array the number of reactions that contain at least one (as opposed to zero) initial template is determined, allowing inferring the original template concentration. Here we present a novel protocol to efficiently infer the concentration of a sample and its optimal dilution for dPCR from few targeted qPCR assays. By taking advantage of the real-time amplification feature of qPCR as opposed to relying on endpoint PCR assessment as in standard dPCR prior knowledge of template concentration is not necessary. This eliminates the need for serial dilutions in a separate titration and reduces the number of necessary reactions. We describe the theory underlying our approach and discuss experimental moments that contribute to uncertainty. We present data from a controlled experiment where the initial template concentration is known as proof of principle and apply our method on directly monitoring transcript level change during cell differentiation as well as gauging amplicon numbers in cDNA samples after pre-amplification. [less ▲]

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See detailRNA-mediated Control of Bacterial Gene Expression: Role of Regulatory non-Coding RNAs
Mandin, Pierre; Toledo-Arana, Alejandro; Fouquier d'Hérouël, Aymeric UL et al

in Meyers, Robert (Ed.) Encyclopedia of Cell and Molecular Biology and Molecular Medicine. RNA Regulation (2013)

Detailed reference viewed: 76 (8 UL)