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Cesareni, G.

Publications and source records attributed to Cesareni, G..

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CausalTab: PSI-MITAB 2.8 updated format for signaling data representation and dissemination

Combining multiple layers of information underlying biological complexity into a structured framework, and in particular deciphering the molecular mechanisms behind cellular phenotypes, represent two challenges in systems biology. A key task is the formalisation of such information in models describing how biological entities interact to mediate the response to external and internal signals. Several databases with signaling information, such as SIGNOR, SignaLink and IntAct, focus on capturing, organising and displaying signaling interactions by representing them as binary, causal relationships between biological entities. The curation efforts that build these individual databases demand a concerted effort to ensure interoperability among resources, through the development of a standardized exchange format, ontologies and controlled vocabularies supporting the domain of causal interactions. Aware of the enormous benefits of standardization efforts in the molecular interaction research field, representatives of the signalling network community agreed to extend the PSI-MI controlled vocabulary to include additional terms representing aspects of causal interactions. Here, we present a common standard for the representation and dissemination of signaling information: the PSI Causal Interaction tabular format (CausalTAB) which is an extension of the existing PSI-MI tab-delimited format, now designated MITAB2.8. We define the new term \"causal interaction\", and related child terms, which are children of the PSI-MI \"molecular interaction\" term. The new vocabulary terms in this extended PSI-MI format will enable systems biologists to model large-scale signaling networks more precisely and with higher coverage than before.

systems biology

Single-cell quantitative analysis of skeletal muscle cell population dynamicsduring regeneration and ageing

The skeletal muscle is populated by a variety of different mononuclear cell types that actively contribute to tissue homeostasis. When the tissue is stressed by exercise or by an acute or chronic insult, the different cell types are activated, exchange signals and initiate a finely-orchestrated regeneration process to prevent the loss of muscle mass. This cell variety is exacerbated by an additional intra population heterogeneity, where the cell population boundaries often lose their significance. Here, we applied a high-dimensional single-cell mass cytometry analysis to solve the cellular and molecular complexity of the muscle tissue in different physiological and pathological conditions. Taken together, our results provide a comprehensive picture both of muscle cell population homeostasis during ageing and of the changes induced by a perturbation of the system, be it chronic (dystrophy) or acute (cardiotoxin).

systems biology

Skeletal muscle fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH-dependent regulation of adipogenesis

Fibro adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fat infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this control mechanism. Nonetheless, factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition. An unbiased mass spectrometry-based proteomic analysis of FAPs from muscles of wild type and mdx mice, revealed that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. These results offer a basis for rationalizing the pathological outcomes of fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fatty depositions in muscles of dystrophic patients.\n\nHighlightsO_LISingle-cell mass cytometry reveals that wt and mdx FAPs are in different cell states.\nC_LIO_LIActivation of the NOTCH signaling pathway negatively regulates adipogenesis of wt but not mdx FAPs.\nC_LIO_LIDeep proteomics suggests a mechanism explaining the different sensitivity of mdx- FAPs to NOTCH.\nC_LIO_LITNF-a stimulation restores the anti-adipogenic effect of NOTCH in mdx FAPs.\nC_LI

cell biology