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Michelbach, A.

Publications and source records attributed to Michelbach, A..

2 recordsLinked to original sources

Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells

Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although signaling circuits and gene regulatory networks that regulate pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations to control state transitions remains a fundamental open question. Here, we focus on two distinct models of pluripotency, primed pluripotent stem cells and pre-implantation inner cell mass cells of human embryos to discover that cell fate transitions associate with rapid changes in nuclear shape and volume which collectively alter the nuclear mechanophenotype. Mechanistic studies in human induced pluripotent stem cells further reveal that these phenotypical changes and the associated active fluctuations of the nuclear envelope arise from growth factor signaling-controlled changes in chromatin mechanics and cytoskeletal confinement. These collective mechano-osmotic changes trigger global transcriptional repression and a condensation-prone environment that primes chromatin for a cell fate transition by attenuating repression of differentiation genes. However, while this mechano-osmotic chromatin priming has the potential to accelerate fate transitions and differentiation, sustained biochemical signals are required for robust induction of specific lineages. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.

cell biology↗

Evidence of active oviposition avoidance to systemically applied imidacloprid in the Colorado Potato Beetle (Leptinotarsa decemlineata)

Agricultural pests can develop behavioral resistance to insecticides via choosing to feed or oviposit on non-toxic hosts. As young larvae have relatively low mobility, oviposition preferences from female adults may play a critical role in shaping the evolutionary trajectory of pest populations. While oviposition avoidance of toxic hosts was found in different agriculture pests, it remains unclear whether such preferences can be learned from female adults. To address this question, we investigated feeding and oviposition preferences to imidacloprid in the Colorado Potato Beetle (CPB, Leptinotarsa decemlineata), a major potato pest. We first identified two CPB strains that have different levels of resistance to imidacloprid. Then, we performed choice assays in the two strains and found that both strains did not have an innate feeding avoidance to systemically applied imidacloprid at both larval and adult stages. Further oviposition choice assays showed that the susceptible strain preferred to lay eggs on insecticide-free plants while the resistant strain did not. Analysing moving patterns of the two strains suggested that the oviposition preference is likely due to active learning by the female adults. Together, these results indicate that CPB can have active oviposition avoidance, which might have contributed to the rapid global invasion of this agricultural pest.

animal behavior and cognition↗