Biology subjects

Tessier, S.

Publications and source records attributed to Tessier, S..

4 recordsLinked to original sources

bioRxiv2024

Optimization of liver graft function using a poly-pharmacological drug cocktail CEPT in a simulated transplant model

BackgroundThe number of patients in need of a liver transplant far exceeds the supply of available organs. This imbalance could be dramatically reduced should the donor organ pool be expanded by rendering marginal cases transplantable rather than discarded. The poly-pharmacological drug cocktail CEPT (Chroman-1, Emricasan, Polyamine, and Trans-ISRIB (integrated stress inhibitor)) has been found to improve the in-vitro viability of human pluripotent stem cells (hPSCs) following cryopreservation. It is worth exploring CEPTs ability to inhibit various apoptotic pathways and preserve cellular function for potentially mitigating warm ischemic stress of the anhepatic phase of graft implantation and promoting more rapid graft recovery following reperfusion with continuous treatment. MethodsRat livers without warm ischemia and CEPT supplementation are the healthy control: fresh (n=3) group. Room-temperature warm ischemia was used to replicate the anhepatic phase of graft implantation in the control (n=6) group and the experimental CEPT group (n=6) without and with CEPT supplementation, respectively. Transplantation was modeled by ex-vivo reperfusion at 37{degrees}C for six hours with Williams E-based hepatocyte culture media and with CEPT supplementation in the CEPT group. ResultsLivers treated with CEPT during warm ischemia and subsequent reperfusion have improved hepatocellular function as indicated by increased oxygen O2 utilization, stable pH, and improved cholangiocyte function indicated by the increased hourly rate of bile production. Furthermore, resistance, an endothelial injury marker, and caspase 3/7, an apoptotic marker, were lower. ConclusionTo improve the utilization of available donor livers, different stages of the organ transplantation process can be optimized. The anhepatic phase, which includes the period from the removal of the native liver from the recipient to the reperfusion of the donors graft liver through the portal vein during graft implantation, can be targeted using CEPT for mitigating warm ischemia-induced injury that occurs during vascular anastomosis. (S1 Fig: Graphical abstract)

bioengineering↗

bioRxiv2021

Unbiased in vivo exploration of nuclear bodies-enhanced sumoylation reveals that PML orchestrates embryonic stem cell fate

Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation, but their role in pluripotency remains elusive. Here we establish that PML is required for basal SUMO2/3 conjugation in mESCs and oxidative stress-driven sumoylation in mESCs or in vivo. PML NBs create an oxidation-protective environment for UBC9-driven SUMO2/3 conjugation of PML partners, often followed by their poly-ubiquitination and degradation. Differential in vivo proteomics identified several members of the KAP1 complex as PML NB-dependent SUMO2-targets. The latter drives functional activation of this key epigenetic repressor. Accordingly, Pml-/- mESCs re-express transposable elements and display features of totipotent-like cells, a process further enforced by PML-controlled SUMO2-conjugation of DPPA2. Finally, PML is required for adaptive stress responses in mESCs. Collectively, PML orchestrates mESC fate through SUMO2-conjugation of key transcriptional or epigenetic regulators, raising new mechanistic hypotheses about PML roles in normal or cancer stem cells.

cell biology↗

bioRxiv2019

Megakaryocytes Display Innate Immune Cell Functions and Respond during Sepsis

Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known participate in immune responses and play significant roles during infections, the role of MKs within the immune system has not been explored. Here we utilize in vitro techniques to show that both cord blood-derived MKs (CB MKs) and MKs from a human megakaryoblastic leukemia cell line (Meg-01) chemotax towards pathogenic stimuli, phagocytose bacteria, and release chromatin webs in response to bacteria. Moreover, in patients with sepsis, we found that MK counts were significantly higher in the peripheral blood, and CD61+ staining was increased in the kidneys and lungs, correlated with the development of organ dysfunction. Overall, our study suggests that MK cells display basic innate immune cell functions and respond during infections and sepsis.

immunology↗

bioRxiv2018

Differential screening identifies molecules specifically inhibiting CCR5 transport to the cell surface and HIV infection

Proteins destined to the cell surface are conveyed through membrane-bound compartments using the secretory pathway. Multiple secretory routes exist in cells, which paves the way to the development of inhibitory molecules able to specifically perturb the transport of a chosen cargo. We used differential high-content screening of chemical libraries to identify molecules reducing the secretion of CCR5, the major co-receptor for HIV-1 entry. Three molecules strongly affected the anterograde transport of CCR5, without inhibiting the transport of the related G protein-coupled receptors CCR1 and CXCR4. These three molecules perturb the transport of endogenous CCR5 and decrease the entry of HIV in human primary target cells. Two molecules were found to share the same mode of action, inhibiting palmitoylation of CCR5. Our results demonstrate that secretory routes can be specifically targeted which allows to envisage novel strategies to provoke the intracellular retention or rerouting of secretory proteins involved in disease development.

cell biology↗