资源环境科技发展态势分析平台

Genetic variations underlying susceptibility to complex autoimmune and allergic diseases are concentrated within noncoding regulatory elements termed enhancers(1). The functions of a large majority of disease-associated enhancers are unknown, in part owing to their distance from the genes they regulate, a lack of understanding of the cell types in which they operate, and our inability to recapitulate the biology of immune diseases in vitro. Here, using shared synteny to guide loss-of-function analysis of homologues of human enhancers in mice, we show that the prominent autoimmune and allergic disease risk locus at chromosome 11q13.5(2-7) contains a distal enhancer that is functional in CD4(+) regulatory T (T-reg) cells and required for T-reg-mediated suppression of colitis. The enhancer recruits the transcription factors STAT5 and NF-kappa B to mediate signal-driven expression of Lrrc32, which encodes the protein glycoprotein A repetitions predominant (GARP). Whereas disruption of the Lrrc32 gene results in early lethality, mice lacking the enhancer are viable but lack GARP expression in Foxp3(+) T-reg cells, which are unable to control colitis in a cell-transfer model of the disease. In human T-reg cells, the enhancer forms conformational interactions with the promoter of LRRC32 and enhancer risk variants are associated with reduced histone acetylation and GARP expression. Finally, functional fine-mapping of 11q13.5 using CRISPR-activation (CRISPRa) identifies a CRISPRa-responsive element in the vicinity of risk variant rs11236797 capable of driving GARP expression. These findings provide a mechanistic basis for association of the 11q13.5 risk locus with immune-mediated diseases and identify GARP as a potential target in their therapy.

Shared synteny guides loss-of-function analysis of human enhancer homologues in mice, identifying a distal enhancer at the autoimmune and allergic disease risk locus at chromosome 11q13.5 whose function in regulatory T cells provides a mechanistic basis for its role in disease.

Interactions between light and an ensemble of strontium atoms in an optical cavity can serve as a testbed for studying dynamical phase transitions, which are currently not well understood.

Interactions between atoms and light in optical cavities provide a means of investigating collective (many-body) quantum physics in controlled environments. Such ensembles of atoms in cavities have been proposed for studying collective quantum spin models, where the atomic internal levels mimic a spin degree of freedom and interact through long-range interactions tunable by changing the cavity parameters(1-4). Non-classical steady-state phases arising from the interplay between atom-light interactions and dissipation of light from the cavity have previously been investigated(5-11). These systems also offer the opportunity to study dynamical phases of matter that are precluded from existence at equilibrium but can be stabilized by driving a system out of equilibrium(12-16), as demonstrated by recent experiments(17-22). These phases can also display universal behaviours akin to standard equilibrium phase transitions(8,23,24). Here, we use an ensemble of about a million strontium-88 atoms in an optical cavity to simulate a collective Lipkin-Meshkov-Glick model(25,26), an iconic model in quantum magnetism, and report the observation of distinct dynamical phases of matter in this system. Our system allows us to probe the dependence of dynamical phase transitions on system size, initial state and other parameters. These observations can be linked to similar dynamical phases in related systems, including the Josephson effect in superfluid helium(27), or coupled atomic(28) and solid-state polariton(29) condensates. The system itself offers potential for generation of metrologically useful entangled states in optical transitions, which could permit quantum enhancement in state-of-the-art atomic clocks(30,31).

The polarization direction of a ferroelectric-like state can be used to control the conversion of spin currents into charge currents at the surface of strontium titanate, a non-magnetic oxide.