Biology subjects

Kissa, K.

Publications and source records attributed to Kissa, K..

6 recordsLinked to original sources

bioRxiv2024

Consequences of Cancer on Zebrafish Danio rerio: Insights into Sex Determination, Sex Ratio, and Offspring Survival.

Offspring sex ratio has been proposed as an indicator of the risk of developing certain cancers in humans, but offspring sex ratio may also be a consequence of the disease. In this study, we delve into this subject using the fish Danio rerio as a model system. First, we explore whether inducing skin cancer at an early stage of the hosts life (embryonic stage) has the potential to influence sex determination and/or sex-specific mortality. Second, we investigate whether the sex ratio in offspring produced by tumor-bearing adult females differs from that of healthy females. Third, we compare the survival (until sexual maturity) of offspring produced by cancerous and non-cancerous females. We found that skin cancer did not influence sex ratio in both experiments. However, consistent with previous studies on other model systems, the survival of offspring from cancerous females was higher, suggesting that diseased females allocate more resources to current reproductive efforts compared to their healthy counterparts. This study makes a significant contribution to our understanding of the ecological and evolutionary consequences of host-tumor interactions in animals.

evolutionary biology↗

bioRxiv2022

The crosstalk between DNA-PK and cGAS drives tumor immunogenicity

Cytosolic DNAs promote inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been thus suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that lack cGAS to question whether alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex drives cGAS independent inflammatory responses but that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote macrophage recruitment in the tumor microenvironment, a process that impaired early tumorigenesis but correlated with poor outcome. Thus, our study supports that cGAS-dependent signaling is acquired during tumorigenesis and that cGAS and DNA-PK activities should be analyzed concertedly to predict the impact of strategies aiming to boost tumor immunogenicity.

cancer biology↗

bioRxiv2021

Investigating pathogenicity and virulence of Staphylococcus pettenkoferi: an emerging pathogen

Staphylococcus pettenkoferi is a coagulase-negative Staphylococcus identified in 2002 that has been implicated in human diseases as an opportunistic pathogenic bacterium. Its multiresistant character is becoming a major health problem, yet the pathogenicity of S. pettenkoferi is poorly characterized. In this study, pathogenicity of a S. pettenkoferi clinical isolate from diabetic foot osteomyelitis was compared to a Staphylococcus aureus strain in various in vitro and in vivo experiments. Growth kinetics were compared against S. aureus and bacteria survival was assessed in the RAW 264.7 murine macrophage cell line, the THP-1 human leukemia monocytic cell line and the HaCaT human keratinocyte cell line. Ex vivo analysis were performed in whole blood survival assays, and in vivo assays via the infection model of zebrafish embryos. Moreover, whole-genome analysis was performed. Our results showed that S. pettenkoferi was able to survive in human blood, human keratinocytes, murine macrophages, and human macrophages. S. pettenkoferi demonstrated its virulence by causing substantial embryo mortality in the zebrafish model. Genomic analysis revealed virulence factors such as biofilm- (e.g., icaABCD; rsbUVW) and regulator- (e.g., agr, mgrA, sarA, saeS) encoding genes well characterized in S. aureus. This study thus advances the knowledge of this under investigated pathogen and validates the zebrafish infection model for this bacterium.

microbiology↗

bioRxiv2021

Endoglin deficiency elicits hypoxia-driven congestive heart failure in zebrafish.

Hereditary hemorrhagic Telangiectasia (HHT) is a rare genetic disease relying on mutations affecting components of Bone Morphogenetic Protein and Transforming Growth Factor-{beta} (BMP/TGF-{beta}) signaling pathway in endothelial cells. This disorder is characterized by arterio-venous malformations prone to rupture. and ensuing hemorrhages are responsible for iron deficiency anemia. Along with Activin receptor-like kinase ALK1, Endoglin is involved in the vast majority of HHT cases. In this report, we characterized zebrafish endoglin locus and demonstrated that it produces two phylogenetically conserved protein isoforms using a distinctive alternative splicing mechanism. Functional analysis of a Crispr/Cas9 zebrafish Endoglin mutant revealed that Endoglin deficiency results in massive death during the course from juvenile stage to adulthood. Endoglin deficient fish develop a cardiomegaly resulting in heart failure and hypochromic anemia which both stem from chronic hypoxia. Histological analysis and confocal imaging evidenced structural alterations of the developing gill and its underlying vascular network that tally with hypoxia. Finally, phenylhydrazine treatment demonstrated that lowering hematocrit/blood viscosity alleviates heart failure and enhances survival of Endoglin deficient fish. Altogether, our data indicate that Endoglin is crucial for gill vascular development and that further studies using zebrafish in general and this endoglin mutant in particular will provide crucial hints regarding the molecular and cellular events altered in HHT for the development of new therapeutic strategies. Summary StatementEndoglin deficiency in zebrafish recapitulates critical aspects of Hereditary Hemorrhagic Telangiectasia (HHT) and will thus constitute a valuable model in large scale screens for HHT-active drugs.

developmental biology↗

bioRxiv2020

Phosphatidylinositol-3 kinase activity controls survival and stemness of zebrafish hematopoietic stem/progenitor cells

Hematopoietic Stem and Progenitor Cells (HSPCs) are multipotent cells giving rise to all blood lineages during life. HSPCs emerge from the ventral wall of the dorsal aorta (VDA) during a specific timespan in embryonic development through endothelial hematopoietic transition (EHT). We investigated the ontogeny of HSPCs in mutant zebrafish embryos lacking functional pten, an important tumor suppressor with a central role in cell signaling. Through in vivo live imaging, we discovered that in pten mutant embryos a proportion of the HSPCs died upon emergence from the VDA, an effect rescued by inhibition of phosphatidylinositol-3 kinase (PI3K). Surprisingly, inhibition of PI3K in wild type embryos also induced HSPC death. Surviving HSPCs colonized the caudal hematopoietic tissue (CHT) normally and committed to all blood lineages. Single cell RNA sequencing indicated that inhibition of PI3K enhanced survival of multi-potent progenitors, whereas the number of HSPCs with more stem-like properties was reduced. At the end of the definitive wave, loss of Pten caused a shift to more restricted progenitors at the expense of HSPCs. We conclude that PI3K signaling tightly controls HSPCs survival and both up- and downregulation of PI3K signaling reduces stemness of HSPCs. 2 Key pointsO_LILoss of Pten and inhibition of PI3K induced apoptosis of hematopoietic stem/progenitor cells upon endothelial to hematopoietic transition C_LIO_LISurviving hematopoietic stem/progenitor cells committed to all blood lineages but displayed reduced stemness C_LI

developmental biology↗

bioRxiv2019

Mechanical instabilities of aorta drive blood stem cell production: a live study

During embryogenesis of all vertebrates, haematopoietic stem/progenitor cells (HSPCs) extrude from the aorta by a complex process named Endothelial-to-Haematopoietic Transition (EHT). HSPCs will then colonize haematopoietic organs allowing haematopoiesis throughout adult life. The mechanism underlying EHT including the role of each aortic endothelial cell within the global aorta dynamics remains unknown. In the present study, we show for the first time that EHT involves the remodelling of individual cells within a collective migration of endothelial cells which is tightly orchestrated, resulting in HSPCs extrusion in the sub-aortic space without compromising aorta integrity. By performing a cross-disciplinary study which combines high resolution 4D imaging and theoretical analysis based on the concepts of classical mechanics, we propose that this complex developmental process is dependent on mechanical instabilities of the aorta preparing and facilitating the extrusion of HSPCs.

developmental biology↗