We report on fabrication of devices integrating FeTe0.55Se0.45 with other van-der-Waals materials, measuring transport properties as well as tunneling spectra at variable magnetic fields and temperatures down to 35 mK. Transport measurements are reliable and repeatable, revealing temperature and magnetic field dependence in agreement with prior results, confirming that fabrication processing does not alter bulk properties. However, cross-section scanning transmission microscopy reveals oxidation of the surface, which may explain a lower yield of tunneling device fabrication. We nonetheless observe hard-gap planar tunneling into FeTe0.55Se0.45 through a MoS2 barrier. Notably, a minimal hard gap of 0.5 meV persists up to a magnetic field of 9 T in the ab plane and 3 T out of plane. This may be the result of very small junction dimensions, or a quantum-limit minimal energy spacing between vortex bound states. We also observed defect assisted tunneling, exhibiting bias-symmetric resonant states which may arise due to resonant Andreev processes.

Background Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains largely unexplained. Results Analyzing single-cell RNA sequencing from Alzheimer’s disease (AD) and Huntington’s disease (HD) patients, we find increased transcriptional heterogeneity in disease-state neurons. We hypothesize that transcriptional heterogeneity precedes neurodegenerative disease pathologies. To test this idea experimentally, we use juvenile forms (72Q; 180Q) of HD iPSCs, differentiate them into committed neuronal progenitors, and obtain single-cell expression profiles. We show a global increase in gene expression variability in HD. Autophagy genes become more stable, while energy and actin-related genes become more variable in the mutant cells. Knocking down several differentially variable genes results in increased aggregate formation, a pathology associated with HD. We further validate the increased transcriptional heterogeneity in CHD8+/− cells, a model for autism spectrum disorder. Conclusions Overall, our results suggest that although neurodegenerative diseases develop over time, transcriptional regulation imbalance is present already at very early developmental stages. Therefore, an intervention aimed at this early phenotype may be of high diagnostic value.

Many neurodegenerative diseases (NDs) develop only later in life, when cells in the nervous system lose their structure or function. In genetic forms of NDs, this late onset phenomenon remains largely unexplained. Analyzing single cell RNA sequencing (scRNA-seq) from Alzheimer disease (AD) patients, we find increased transcriptional heterogeneity in AD excitatory neurons. We hypothesized that transcriptional heterogeneity precedes ND pathologies. To test this idea experimentally, we used juvenile forms (72Q; 180Q) of Huntington disease (HD) iPSCs, differentiated them into committed neuronal progenitors, and obtained single cell expression profiles. We show a global increase in gene expression variability in HD. Autophagy genes become more stable, while energy and actin-related genes become more variable in the mutant cells. Knocking-down several differentially-variable genes resulted in increased aggregate formation, a pathology associated with HD. We further validated the increased transcriptional heterogeneity in CHD8+/- cells, a model for autism spectrum disorder. Overall, our results suggest that although NDs develop over time, transcriptional regulation imbalance is present already at very early developmental stages. Therefore, an intervention aimed at this early phenotype may be of high diagnostic value.