Typologie d'actualités: CBM

Conference by Prof. Ken LAU and Dr Andrea ROLONG – June 5, 2023

This international conference is organized within the framework of the ARD CVL Biomedicaments Program.

Abstract: Tissue complexity emerges from interactions of components across various biological systems, such as exogenous factors from the microbiota and different types of host cells, and the body's immune cells to the presence of tumors. These interactions occur across genetic, molecular, and spatial domains. Although single-cell and spatial -omics approaches are already capable of profiling various components at an atlas scale, there is still a significant gap in effectively transforming these methods from correlative studies to hypothesis-driven studies. Here, we present two stories on how-omic level data and computational analyzes can be integrated with experimental models (human, mouse, and organoid) for mechanistic studies:

- in understanding rare epithelial cell populations in modulating inflammation in the gut,

- in modeling a pre-cancer-to-cancer transition in the colon. We present emerging techniques, analyses, and the key roles they play in understanding the complex interactions that dictate tissue function in homeostasis and disease.

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Truly life materials?

Physiological characterization of life in Engineered Living Materials by confocal microscopy at single cell resolution.

The CNRS Institute of Chemistry reported this remarkable research on its site. See the article

Engineered Living Materials (ELMs) combine living cells with non-living scaffolds to get life-like characteristics, such as biosensing, growth, and self-repair. Some ELMs are 3D-printed, and called bio-ink. For ELMs to be functional, cells in ELMs has to remain alive and active. However, currently, microorganism physiology in ELMs is still elusive and restrict their use.

Researchers of the team "Cell signalling and neurofibromatosis" reconstituted such bioprinted ELMs by associating the yeast Saccharomyces cerevisiae with the hydrogel Pluronic F-127. Theydeveloped genetically engineered yeast by integrating fluorescent gene whose expression is correlated to a physiological parameter: ATP concentration (metabolism), intracellular pH (growth phase), morphology … These engineered and ratiometric biosensors are effective and allow to assess yeast physiological status in ELM directly in situ by confocal microscopy at single cell scale level. They constitute a valuable tool easy to adapt to any other system by associating them to other materials to evaluate their biocompatibility.

Furthermore, the researchers tested their recently developed copper biosensor embedded into this hydrogel F-127, and showed it is fully functional into this ELM. Yeast biosensor association with hydrogel provides several very interesting advantages such as protecting yeast from contaminations and supplying them with nutrients.

This work allows to establish the proof of concept that F127 associated with engineered yeast S. cerevisiae is a promising ELM in order to develop easy to use whole-cell biosensors able to detect copper directly on samples collected in the environment.

Bojan Žunar B., Ito T., Mosrin C., Sugahara Y., Bénédetti H., Guégan R. and Vallée B.
Confocal imaging of biomarkers at a single-cell resolution: quantifying 'living' in 3D-printable engineered living material based on Pluronic F-127 and yeast Saccharomyces cerevisiae.
Biomater Res 26, 85 (2022). https://doi.org/10.1186/s40824-022-00337-8

Milk thistle, a plant extract with promising –green- medicinal properties against psoriasis

Considering the relative low efficacy and high toxicity of current drug treatments against psoriasis, new therapeutic strategies are needed.

Scientists from CBM have searched for natural products unable to modulate the TGFb/miRNA-21-5p pathway in keratinocyte cells. This axis of regulation was chosen not only because it plays a pivotal role in epidermal haemostasis but also because its dysregulation is systematically associated with skin disorders including psoriasis.

To identify such bioactive compounds, a library of medicinal plant extracts was screened using the miR-ON RILES screening system placed under the control of the miRNA-21-5p in keratinocytes treated with TGFb. Silymarin, a mixture of flavonolignans extracted from Silybum marianum (L.) Gaertn., was identified as the most potent regulator of miRNA-21-5p expression. RNA-sequencing analysis revealed three unexpected transcriptomic signatures associated with keratinocyte differentiation, cell cycle, and lipid metabolism.

Mechanistically, Silymarin blocks cell cycle progression, inhibits keratinocyte differentiation through repression of Notch3 expression, stimulates lipid synthesis via activation of PPARg signaling and inhibits inflammatory responses by suppressing the transcriptional activity of NF-kB. Notably, the topical application of silymarin alleviates the development of psoriasiform lesions in mice by abrogating the altered expression levels of markers involved in inflammation, proliferation, differentiation, and lipid metabolism without inducing toxicity.

Therefore this plant extract might represent a promising "green" alternative to current pharmacological treatments for the management of this pathology.


Elodie Henriet,Florence Abdallah, Yoan Laurent, Cyril Guimpied, Emily Clement, Michel Simon, Chantal Pichon and Patrick BarilTargeting TGF-β1/miR-21 Pathway in Keratinocytes Reveals Protective Effects of Silymarin on Imiquimod-Induced Psoriasis Mouse ModelVolume 3, ISSUE 3, 100175, May 2023 - DOI:https://doi.org/10.1016/j.xjidi.2022.100175