Biology subjects

Benderitter, M.

Publications and source records attributed to Benderitter, M..

3 recordsLinked to original sources

bioRxiv2024

The DNA damage response relies on the characteristics of ionizing particles in myogenic cells

DNA integrity and stability are vital for proper cellular activity. Nevertheless, to treat cancer patients, DNA is the main target for inducing tumoral cell death. Nowadays, cancer treatment is improving by the development of new technologies, protocols and strategies. Amongst them, the charged particle radiotherapies are becoming prevalent. However, tumor-neighboring healthy tissues are still exposed to ionizing radiations (IR) and subject to late side effects. Skeletal muscle is one of those tissues most likely to be affected. To decipher the DNA damage response (DDR) of skeletal muscle cells, myogenic cells, we irradiated them with microbeams of protons or -particles and followed the accumulation of DDR proteins at localized irradiation sites. Thereby, we showed that myoblasts, proliferating myogenic cells, repair local IR-induced DNA damage through both non-homologous end-joining and homologous recombination with different recruitment dynamics depending on the characteristics of ionizing particles (type, energy deposition and time after irradiation), whereas myotubes, post-mitotic myogenic cells, display globally reduced DNA damage response.

cell biology↗

bioRxiv2019

Effects of repetitive Iodine Thyroid Blocking on the Development of the Foetal Brain and Thyroid in rats: a Systems Biology approach

A single dose of potassium iodide (KI) against repeated exposure to radioactive iodine, such as the one of the Fukushima accident, might not be effective enough to protect the thyroid. Our group showed that repetitive dose of KI for eight days offers efficient protection without toxic effects in adult rats. However, the effect of repetitive KI on the developing foetus still unknown especially on brain development, but a correlation between the impaired maternal thyroid status and a decrease in intelligence quotient has been observed. In this study, gene expression analysis of the progeny of repetitive KI-administered pregnant rats performed by our group showed distinct gene expression profile from two different organs: thyroid and cortex. To understand how these differentially expressed genes are implicated in the observed behaviour change, a systems biology approach was used to construct networks using three different techniques; Bayesian statistics using ShrinkNet, sPLS-DA on the DIABLO platform using mixOmics and manual construction of a Process Descriptive network. For each organ, we were able to construct gene expression network, to select genes that are most contributing to either control or KI-treated groups, respectively, and to construct the PD network from differentially expressed (DE) gene enriched with data from publications. Furthermore, we were able to connect DE genes from both organs into one network with genes from both organ participating in the same cellular processes that affect mitophagy and neuronal outgrowth.\n\nThis work may help to evaluate the doctrine for using KI in case of repetitive or prolonged exposure to radioactive particles upon nuclear accidents.

systems biology↗

bioRxiv2017

Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells

Introductory paragraphThe successful production of Hematopoietic Stem and Progenitor Cells (HSPCs) from human pluripotent sources is conditioned by transgene delivery1-5. We describe here a dedicated and tractable one step, GMP-grade, transgene-free and stroma-free protocol to produce HSPCs from human induced pluripotent stem cells (hiPSCs). This procedure, applied to several sources of hiPSCs with equal efficiency, is based on a directed differentiation with morphogens and cytokines to generate a cell population close to nascent HSPCs or their immediate forerunners i.e., hemogenic endothelial cells6-9. Following engraftment into immunocompromised recipients, this cell population was proved capable of a robust myeloid, lymphoid and definitive red blood cell production in sequential recipients for at least 40 weeks. Further identification of the repopulating cells show that they express the G protein-coupled receptor APELIN (APLNR) and the homing receptor CXCR4. This demonstrates that the generation of bona fide HSPCs from hiPSCs without transgenes is possible and passes through an early endo-hematopoietic intermediate. This work opens the way to the generation of clinical grade HSPCs for the treatment of hematological diseases and holds promise for the analysis of HSPC development in the human species.

cell biology↗