A nuclear pore-anchored condensate enables germ granule organization and transgenerational epigenetic inheritance
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Transgenerational inheritance of diabetes susceptibility in male offspring with maternal androgen exposure
Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet. Mechanistically, compromised insulin secretion underlies this transgenerational susceptibility to diabetes. Integrated analyses of methylome and transcriptome revealed differential DNA methylation of β-cell functional genes in AE-F1 sperm, which was transmitted to AE-F2 islets and further retained in AE-F2 sperm, leading to reduced expression of genes related to insulin secretion, including Pdx1, Irs1, Ptprn2, and Cacna1c. The methylation signatures in AE-F1 sperm were corroborated in diabetic humans and the blood of sons with maternal hyperandrogenism. Moreover, caloric restriction and metformin treatments normalized hyperglycemia in AE-F1 males and blocked their inheritance to offspring by restoring the aberrant sperm DNA methylations. Our findings highlight the transgenerational inheritance of impaired glucose homeostasis in male offspring from maternal AE via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations’ metabolic health.
Coherence of a non-equilibrium polariton condensate across the interaction-mediated phase transition
The emergence of spatial coherence in a confined two-dimensional Bose gas of exciton polaritons with tuneable interactions offers a unique opportunity to explore the role of interactions in a phase transition in a driven-dissipative quantum system, where both the phase transition and thermalisation are mediated by interactions. We investigate, experimentally and numerically, the spatial coherence and steady-state properties of the gas over a wide range of interaction strengths by varying the photonic/excitonic fraction of the polaritons and their density. We find that the first order spatial correlation function exhibits algebraic decay consistent with the Berezinskii-Kosterlitz-Thouless (BKT) phase transition. The exponent of the algebraic decay is inversely proportional to the coherent fraction of polaritons, in analogy to superfluid fraction of equilibrium quantum gases above the BKT transition, but with a different proportionality constant. Our work paves the way for future investigations of the phenomenon of phase transitions and superfluidity in a driven-dissipative setting.
A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan
Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes.
Personalized bioceramic grafts for craniomaxillofacial bone regeneration
The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue formation, making them ideal as synthetic grafts. This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction. In this regard, clinically relevant topics such as ceramic-based biomaterials, graft/scaffold characteristics (macro/micro-features), material extrusion-based 3D printing, and the step-by-step workflow to engineer personalized bioceramic grafts are discussed. Importantly, in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior. Lastly, we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.
Paternal heroin self-administration in rats increases drug-seeking behavior in male offspring via miR-19b downregulation in the nucleus accumbens
Accumulating evidence indicates that drug addiction may lead to adaptive behavioral changes in offspring, potentially due to epigenetic modifications in parental germline. However, the underlying mechanisms remain inadequately understood. In this study, we show that paternal heroin self-administration (SA) increased heroin-seeking behavior in the F1 generation, when compared with offspring sired by yoke-infused control males, indicating cross-generational impact of paternal voluntary heroin seeking behavior. Notably, the increase of heroin seeking behavior in offspring was replicated by zygotic microinjection of sperm RNAs derived from sperm of heroin-SA-experienced rats. Analysis of non-coding RNAs in spermatozoa revealed coordinated changes in miRNA content between the nucleus accumbens and spermatozoa. We validated that restoration of miR-19b downregulation in sperm RNA from self-administration-experienced rats, in parallel with its overexpression in the nucleus accumbens of F1 offspring sired by heroin-SA-experienced fathers, reversed the increased heroin SA observed in these F1 offspring. Taken together, our findings suggest in rats that paternal heroin self-administration induces epigenetic changes in both brain and sperm miRNA, with miR-19b downregulation playing a critical role in mediating the epigenetic inheritance of increased heroin self-administration behavior in the F1 generation.
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