MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode.

Mutations in human MAB21L1 cause aberrations in lens ectoderm morphogenesis and lead to congenital cerebellar, ocular, craniofacial and genital (COFG) syndrome. Murine Mab21l1-null mutations cause severe cell-autonomous defects in lens formation, leading to microphthalmia; therefore, Mab21l1-null mice are used as a mouse model for COFG syndrome. In this study, we investigated the early-onset single-cell-level phenotypes of murine Mab21l1-null lens ectoderms using electron microscopy and single-cell RNA sequencing (scRNA-seq). Electron microscopy and immunohistochemical analyses indicated endoplasmic reticulum stress at the 24- to 26-somite stage in Mab21l1-null lens placodes. scRNA-seq analysis revealed that 131 genes were downregulated and 148 were upregulated in Mab21l1-null lens ectoderms relative to the wild type. We successfully identified 21 lens-specific genes that were downregulated in Mab21l1-null cells, including three key genes involved in lens formation: Pitx3, Maf and Sfrp2. Moreover, gene ontology analysis of the 279 differentially expressed genes indicated enrichment in housekeeping genes associated with DNA/nucleotide metabolism prior to cell death. These findings suggest that MAB21L1 acts as a nuclear factor that modulates not only lens-specific gene expression but also DNA/nucleotide metabolic processes during lens placode formation.

Three-body correlations in nonlinear response of correlated quantum liquid.

Behavior of quantum liquids is a fascinating topic in physics. Even in a strongly correlated case, the linear response of a given system to an external field is described by the fluctuation-dissipation relations based on the two-body correlations in the equilibrium. However, to explore nonlinear non-equilibrium behaviors of the system beyond this well-established regime, the role of higher order correlations starting from the three-body correlations must be revealed. In this work, we experimentally investigate a controllable quantum liquid realized in a Kondo-correlated quantum dot and prove the relevance of the three-body correlations in the nonlinear conductance at finite magnetic field, which validates the recent Fermi liquid theory extended to the non-equilibrium regime.

Single-cell transcriptional analysis reveals developmental stage-dependent changes in retinal progenitors in the murine early optic vesicle.

The optic vesicle in the developing embryonic eye contains a multitude of neuroepithelial progenitors that subsequently differentiate into functionally distinct domains of the optic cup, such as the neural retina, pigment epithelium, and optic stalk. To investigate cell-type diversity across early optic vesicles before regionalization of the optic cup, we performed single-cell RNA-sequencing (scRNA-seq) using 7989 cells from the presumptive eye area in mouse embryos at the 12-26-somite stages at five developmental time points. We demonstrated the presence of seven optic vesicle populations. Moreover, the four populations of retinal progenitor cells could be classified according to their stage-dependent time point, and these cells exhibited altered expression of several structural and metabolic key genes, such as Col9a1 and Ckb, just before regionalization of the optic cup. From these data, we provide the first report on stage-dependent transcriptional profiles during initial retinal specification at single-cell resolution and highlight the unexpected developmental heterogeneity of the murine optic vesicle structure.

Fermi Liquid Theory for Nonlinear Transport through a Multilevel Anderson Impurity.

We present a microscopic Fermi liquid view on the low-energy transport through an Anderson impurity with N discrete levels, at arbitrary electron filling N_{d}. It is applied to nonequilibrium current fluctuations, for which the two-quasiparticle collision integral and the three-body correlations that determine the quasiparticle energy shift play important roles. Using the numerical renormalization group up to N=6, we find that for strong interactions the three-body fluctuations are determined by a single parameter other than the Kondo energy scale in a wide filling range 1≲N_{d}≲N-1. It significantly affects the current noise for N>2 and the behavior of noise in magnetic fields.

Higher-Order Fermi-Liquid Corrections for an Anderson Impurity Away from Half Filling.

We study the higher-order Fermi-liquid relations of Kondo systems for arbitrary impurity-electron fillings, extending the many-body quantum theoretical approach of Yamada and Yosida. It includes, partly, a microscopic clarification of the related achievements based on Nozières' phenomenological description: Filippone, Moca, von Delft, and Mora [Phys. Rev. B 95, 165404 (2017)PRBMDO2469-995010.1103/PhysRevB.95.165404]. In our formulation, the Fermi-liquid parameters such as the quasiparticle energy, damping, and transport coefficients are related to each other through the total vertex Γ_{σσ^{'};σ^{'}σ}(ω,ω^{'};ω^{'},ω), which may be regarded as a generalized Landau quasiparticle interaction. We obtain exactly this function up to linear order with respect to the frequencies ω and ω^{'} using the antisymmetry and analytic properties. The coefficients acquire additional contributions of three-body fluctuations away from half filling through the nonlinear susceptibilities. We also apply the formulation to nonequilibrium transport through a quantum dot, and clarify how the zero-bias peak evolves in a magnetic field.

Involvement of the Mab21l1 gene in calvarial osteogenesis.

The Mab-21 gene family is crucial for animal development. A deficiency in the Mab-21 genes associates with several defects, including skeletal malformation in mice and humans. In this study, we observed that mice lacking Mab21l1 displayed an unclosed fontanelle, suggesting impaired calvarial bone development. Cells isolated from the calvaria of these mice showed a greater osteoblast differentiation potential as evidenced by the abundance of mineralized bone nodules and higher expression levels of osteogenic markers than wild-type cells. Mab21l1-/- osteoblasts also expressed higher levels of adipocyte genes and interferon-regulated genes at early stages of osteogenesis. Rankl/Opg expression levels were also higher in Mab21l1-/- osteoblasts than in wild-type cells. These data suggest that Mab21l1 is involved in either the regulation of mesenchymal cell proliferation and differentiation or the balance between bone formation and resorption. An alteration in these regulatory machineries, therefore, may lead to insufficient bone formation, causing the bone phenotype in Mab21l1-/- mice.

Quantum Fluctuations along Symmetry Crossover in a Kondo-Correlated Quantum Dot.

Universal properties of entangled many-body states are controlled by their symmetry and quantum fluctuations. By the magnetic-field tuning of the spin-orbital degeneracy in a Kondo-correlated quantum dot, we have modified quantum fluctuations to directly measure their influence on the many-body properties along the crossover from SU(4) to SU(2) symmetry of the ground state. High-sensitive current noise measurements combined with the nonequilibrium Fermi liquid theory clarify that the Kondo resonance and electron correlations are enhanced as the fluctuations, measured by the Wilson ratio, increase along the symmetry crossover. Our achievement demonstrates that nonlinear noise constitutes a measure of quantum fluctuations that can be used to tackle quantum phase transitions.

Full counting statistics for orbital-degenerate impurity Anderson model with Hund's rule exchange coupling.

We study nonequilibrium current fluctuations through a quantum dot, which includes a ferromagnetic Hund's rule coupling J, in the low-energy Fermi liquid regime using the renormalized perturbation theory. The resulting cumulant for the current distribution in the particle-hole symmetric case shows that spin-triplet and spin-singlet pairs of quasiparticles are formed in the current due to the Hund's rule coupling, and these pairs enhance the current fluctuations. In the fully screened higher-spin Kondo limit, the Fano factor takes a value F(b)=(9M+6)/(5M+4) determined by the orbital degeneracy M. We also investigate the crossover between the small and large J limits in the two-orbital case M=2, using the numerical renormalization group approach.