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Hesnard, J.

Publications and source records attributed to Hesnard, J..

3 recordsLinked to original sources

Dictyostelium discoideum chemotaxis is altered by hypoxia to orient streaming toward higher oxygen level independently of aerotaxis.

BackgroundDictyostelium discoideum (Dd) exhibits a unique life cycle marked by its transition from single-cell amoeboid movement to multicellular development in response to environmental stimuli. While its chemotactic response to cyclic adenosine monophosphate (cAMP) has been extensively studied, experiments are usually carried out in a high oxygen environment (21% O2, also called normoxia) that might not reflect the natural condition for a soil amoeba as hypoxia is common underground. Our recent research has unveiled a novel phenomenon termed aerotaxis, wherein Dd cells migrate towards oxygen-rich environments under low oxygen (hypoxia). ResultsWe tested Dd response when submitted to two different stress sources: starvation and hypoxia. While both stresses induce a motile response, namely chemotaxis and aerotaxis, we were able to decoupled both type of responses to explore potential shared mechanisms. Importantly, aerotaxis appears to be operated independently of known chemotactic pathways, demonstrating unique signaling pathways and cellular responses. Aerotaxis contributes to Dd developmental processes by letting cells escape from acute hypoxia. Even though chemotactic response can occur at less than 2% O2, it does not lead to well organized or stable streaming. Furthermore, in an oxygen gradient, aggregation center for chemotactic response appears preferentially at higher O2 level. RT-qPCR analysis show that hypoxia only slightly reduces the expression of genes required for chemotactic response, suggesting that the bias toward high O2 might occur at another level. Reoxygenation of cells that have been starved in hypoxic condition for 18h allow rapid aggregation but require de novo protein synthesis. ConclusionAerotaxis and chemotaxis mechanisms do not interact directly. However, when cells are exposed to both hypoxia and starvation, both mechanisms can be combined to direct the migration of cells toward place with higher oxygen level. As hypoxia is frequent in the soil where Dd usually grow, formation of aggregation centers at, or close to the soil surface, where oxygen is abundant, will be advantageous. Low O2 level does not preclude cells to participate to streaming but seems to reduce or delay their ability to produce stable aggregation centers, resulting into bias favoring centers that form at higher oxygen level.

cell biology↗

Global characterization of Dictyostelium discoideum gene expression changes under hypoxic conditions

Aerobic eukaryotes utilize O2 to oxidize metabolites and generate ATP. The protist kingdom lacks the Hypoxia Inducible Factor-dependent transcriptional response network to accommodate low O2 though possesses a HIF prolyl hydroxylase that initially mediates the response. To address the scale and scope of hypoxic responses in protists, we characterized transcriptomic and proteomic changes when the social amoeba Dictyostelium is subjected to low (1%) O2 under nutritive conditions over 24 h followed by reoxygenation. Remarkably, 32% of the transcripts quantified were differentially expressed during hypoxia, with greatest changes associated with early (1 h) and late phases (24 h). Protein changes were modestly correlated with and generally lagged behind transcriptional changes. Correlated changes were observed for transcripts and proteins associated with various metabolic, anabolic, and catabolic pathways, as well as chromosome organization, cell cycling, vesicular trafficking, and signaling. Analysis of 4 marker genes showed extremely rapid responses that were graded over a range of O2 levels, with differential responses to inhibitors affecting protein synthesis and mitochondria. Overall, the amoebal response to a low but non-toxic O2-level resulted in massive remodeling of the transcriptome and proteome.

genomics↗

Microphase separation of living cells

Self-organization of cells is central to a variety of biological systems and physical concepts of condensed matter have proven instrumental in deciphering some of their properties. Here we show that microphase separation, long studied in polymeric materials and other inert systems, has a natural counterpart in living cells. When placed below a millimetric film of liquid nutritive medium, a quasi two-dimensional, high-density population of Dictyostelium discoideum cells spontaneously assemble into compact domains. Their typical size of 100 m is governed by a balance between competing interactions: an adhesion acting as a short-range attraction and promoting aggregation, and an effective long-range repulsion stemming from aerotaxis in near anoxic condition. Experimental data, a simple model and cell-based simulations all support this scenario. Our findings establish a generic mechanism for self-organization of living cells and highlight oxygen regulation as an emergent organizing principle for biological matter.

biophysics↗