Organ donation | EPFL Graph Search

Organ donation is the process when a person allows an organ of their own to be removed and transplanted to another person, legally, either by consent while the donor is alive or dead with the assent of the next of kin. Donation may be for research or, more commonly, healthy transplantable organs and tissues may be donated to be transplanted into another person. Common transplantations include kidneys, heart, liver, pancreas, intestines, lungs, bones, bone marrow, skin, and corneas. Some organs and tissues can be donated by living donors, such as a kidney or part of the liver, part of the pancreas, part of the lungs or part of the intestines, but most donations occur after the donor has died. In 2019, Spain had the highest donor rate in the world at 46.91 per million people, followed by the US (36.88 per million), Croatia (34.63 per million), Portugal (33.8 per million), and France (33.25 per million). As of February 2, 2019, there were 120,000 people waiting for life-saving organ transplants in the US. Of these, 74,897 people were active candidates waiting for a donor. While views of organ donation are positive, there is a large gap between the numbers of registered donors compared to those awaiting organ donations on a global level. To increase the number of organ donors, especially among underrepresented populations, current approaches include the use of optimized social network interventions, exposing tailored educational content about organ donation to target social media users. Every year August 13 is observed as World Organ Donation Day to raising awareness about the importance of organ donation. Organ donors are usually dead at the time of donation, but may be living. For living donors, organ donation typically involves extensive testing before the donation, including psychological evaluation to determine whether the would-be donor understands and consents to the donation. On the day of the donation, the donor and the recipient arrive at the hospital, just like they would for any other major surgery.

A Baseline Cellular Antiviral State Is Maintained by cGAS and Its Most Frequent Naturally Occurring Variant rs610913

Jacques Fellay, Christian Axel Wandall Thorball, Shuting Xu

Upon recognition of aberrantly located DNA, the innate immune sensor cyclic GMP-AMP synthase (cGAS) activates stimulator of IFN genes (STING)/IFN regulatory factor (IRF)3-driven antiviral responses. In this study, we characterized the ability of a specific variant of the human cGAS-encoding gene MB21D1, rs610913, to alter cGAS-mediated DNA sensing and viral infection. rs610913 is a frequent G>T polymorphism resulting in a P261H exchange in the cGAS protein. Data from the International Collaboration for the Genomics of HIV suggested that rs610913 nominally associates with HIV-1 acquisition in vivo. Molecular modeling of cGAS(P261H) hinted toward the possibility for an additional binding site for a potential cellular cofactor in cGAS dimers. However, cGAS(wild-type [WT]) or cGAS(P261H)-reconstituted THP-1 cGAS knockout cells shared steady-state expression of IFN-stimulated genes, as opposed to cells expressing the enzymatically inactive cGAS(G212A/S(213)A). Accordingly, cGAS(WT) and cGAS(P261H) cells were less susceptible to lentiviral transduction and infection with HIV-1, HSV-1, and Chikungunya virus as compared with cGAS knockout or cGAS(G212A/S(213)A) cells. Upon DNA challenge, innate immune activation appeared to be mildly reduced upon expression of cGAS(P261H) compared with cGAS(WT). Finally, DNA challenge of PBMCs from donors homozygously expressing rs610913 provoked a trend toward a slightly reduced type I IFN response as compared with PBMCs from GG donors. Taken together, the steady-state activity of cGAS maintains a baseline antiviral state rendering cells more refractory to IFN-stimulated gene-sensitive viral infections. rs610913 failed to grossly differ phenotypically from the WT gene, suggesting that cGAS(P261H) and WT cGAS share a similar ability to sense viral infections in vivo.

AMER ASSOC IMMUNOLOGISTS2022

Expansion of a VE-Cadherin+CD45+ population in the yolk sac upon Etv2 overexpression in the mouse embryo - Effects of BMP and Wnt signaling inhibition on the differentiation of a Flk1+ extraembryonic mesoderm in vitro model

Matteo Pluchinotta

The difficulty to find compatible donors for bone marrow transplantation makes the need for an alternative source of HSCs urgent. HSC derived from patient-specific iPS cells are ideal candidates for this purpose. Nevertheless, although HSCs are the best characterized adult stem cells, the in vitro generation and expansion of bone fide HSCs still has not been achieved without transgene insertion. Successful derivation of HSCs from ES cells or iPS cells will require a comprehensive understanding of inductive signals and downstream effectors involved in the normal arising of HSCs during embryonic development. BMP and Wnt signaling pathways play a very important role in this differentiation process. Here, we report how BMP and Wnt signaling inhibition cooperatively alter the differentiation of Flk1+PDGFRα- cells after reculture in serum-free, feeder layer-free conditions. This data will be useful in determining the factors that have to be added to a chemically defined culture medium aimed at derivation of bone fide HSC in vitro. In the second part of this master’s project, we studied the spatial and temporal localization requirements of Etv2 expression, a key regulator of the earliest events in the development of the hematopoietic and vascular systems. To gain more insight on this matter, we conditionally knocked-in Etv2 in the early endothelial compartment, using a Tie2Cre system. This leaded to an embryonically lethal phenotype by E11.5, and most interestingly, to the expansion of a VE-Cadherin+CD45+ population in the E10.5 yolk sac. We believe that these cells represent a increased pool of immature pre-definitive hematopoietic stem cells, thus underlining further the importance of Etv2 in the differentiation process towards hematopoietic, and endothelial lineages in the mouse embryo.

2011

Matteo Pluchinotta

2011

A Baseline Cellular Antiviral State Is Maintained by cGAS and Its Most Frequent Naturally Occurring Variant rs610913

Jacques Fellay, Christian Axel Wandall Thorball, Shuting Xu

AMER ASSOC IMMUNOLOGISTS2022