Theoretical Design of Blue-Color Phosphorescent Complexes for Organic Light-Emitting Diodes: Emission Intensities and Nonradiative Transition Rate Constants in Ir(ppy)2(acac) Derivatives.

Theoretical calculations of phosphorescent spectra and nonradiative transition (NRT) rate constants for S1 ⇝ T1, T1 ⇝ S0, and S1 ⇝ S0 were carried out to determine the best candidate for a blue-color phosphorescent complex among several derivatives of bis(2-phenylpyridine)(acetylacetonate)iridium(III). The geometries of the ground state (S0), the lowest triplet state (T1), and the lowest excited singlet state (S1) were optimized at the levels of density functional theory, in which B3LYP functionals and SBKJC+p basis sets were used. The NRT rate constants were derived by using a generating function method within the displaced harmonic oscillator model. The results of the calculation for phosphorescence showed that the introduction of F and/or CN substituents at the 4'/6'-th and 5'-th sites in 2-phenylpyridinate (ppy) ligands, respectively, causes a blue shift of the emission spectra. They also suggest that Ir(5-CN,6-F-ppy)2(acac), denoted 3(56) in the text, is a good candidate for a blue-color phosphorescent complex because a blue shift of emission spectra and a moderate intensity are obtained for phosphorescence and, furthermore, this complex is calculated to have a large rate constant for S1 ⇝ T1 and relatively smaller rate constants for T1 ⇝ S0 and S1 ⇝ S0 based on the calculations of spin-orbit coupling and nonadiabatic coupling constants.

Theoretical Study of Dynamic Stark-Induced π-Electron Rotations in Low-Symmetry Aromatic Ring Molecules beyond the Frozen Nuclear Approximation.

The effects of vibrational motions on dynamic Stark-induced π-electron rotations in a low-symmetry aromatic ring molecule are theoretically studied in the adiabatic approximation. We adopt a simplified three-electronic state model with a few vibronic states. A pair of the lowest vibronic states in two electronic excited states is set degenerate by irradiation of two linearly polarized UV lasers. The resultant degenerate state is named the dynamic Stark-induced degenerate vibronic state (DSIDVS). The laser parameters (intensities and central frequencies) are determined under the conditions of DSIDVS formation. The aromatic ring molecules of interest are supposed to belong to the weak coupling case. The analytical expressions for the DSIDVS and coherent angular momentum LZ(t) are derived in the displaced harmonic oscillator (DHO) model. Two horizontal potential displacements (δα, δß) between the two electronic excited states (α and ß) and the ground state are the parameters in the DHO model. The LZ(t) calculated with δα = 뫧 is characterized by a regular sequence of the angular momentum pulses with a positive (or negative) constant. For a more general case with δα ≠ δß, the regular sequence is broken down because of the contribution of the first excited vibronic state in each electronic state to LZ(t).

Dynamic Stark-Induced Coherent π-Electron Rotations in a Chiral Aromatic Ring Molecule: Application to Phenylalanine.

We present the results of a theoretical study on dynamic Stark-induced coherent π-electron rotations in a chiral aromatic ring molecule. This is an extension of our previous papers, which have been published in Mineo , H. [ Phys. Chem. Chem. Phys. 2016 , 18 , 26786 - 26795 ] and Mineo , H. [ J. Phys. Chem. Lett. 2018 , 9 , 5521 - 5526 ]. In those papers, the time-dependent Schrödinger equation was solved under a restricted condition in which a degenerate excited state should be formed at the center of the two relevant excited states by dynamic Stark effects. The dynamic Stark-induced degenerate state (DSIDS) is essential to create unidirectional π-electron rotations. In the present theoretical treatment, the above restriction is relaxed and the DSIDS is set to be at any energy position between the two excited states. This indicates a wide applicability of the dynamic Stark effects to coherent control of photophysical properties in aromatic molecules, such as coherent ring currents and current-induced magnetic fluxes of low-symmetric aromatic molecules. Analytical expressions for the coherent π-electron angular momentum are derived within a three-electronic-state model by using the Laplace transform method. The validity of the developed theoretical procedure is demonstrated by carrying out simulations of the coherent angular momentum of l-phenylalanine. Effects of varying the DSIDS on the time-dependent coherent angular momentum and the populations in the three electronic states are examined, and the results are analyzed using approximate expressions for the time-dependent coherent angular momentum and the populations. Modulations in the time-dependent coherent angular momentum appear when the DSIDS is set at an energy position between the two excited states, while there are no beating modulations when the DSIDS is set at the center position. Such differences originate from whether interferences between the two dressed states take place or not.

Quantum Design for Ultrafast Probing of Molecular Chirality through Enantiomer-Specific Coherent π-Electron Angular Momentum.

Probing molecular chirality, right-handed or left-handed chiral molecules, is one of the central issues in chemistry and biochemistry. The conventional theory of optical activity measurements such as circular dichroism has been derived in the second-order processes involving electric and magnetic dipole moments, and the signals are very weak. We propose an efficient enantiomer-probing scenario for chiral aromatic ring molecules based on photoinduced coherent π-electron rotations. In our model, the resultant laser-induced currents themselves produce a strong magnetic field. The principle for probing molecular chirality is a utilization of dynamic Stark effects of two electronic excited states. These electronic states subjected to strong nonresonant linearly polarized UV lasers become degenerate to create enantiomer-specific electronic angular momentum. A pair of enantiomers of phenylalanine was taken as an example. Enantiomer-specific coherent magnetic fluxes on the order of a few teslas can be generated in several tens of femtoseconds. The direct detection of strong coherent magnetic fluxes could be carried out by time-resolved magnetic force microscopy experiments. The results provide important implications for the measurement of effective probing of chiral aromatic molecules.

Quantum control of coherent π-electron ring currents in polycyclic aromatic hydrocarbons.

We present results for quantum optimal control (QOC) of the coherent π electron ring currents in polycyclic aromatic hydrocarbons (PAHs). Since PAHs consist of a number of condensed benzene rings, in principle, there exist various coherent ring patterns. These include the ring current localized to a designated benzene ring, the perimeter ring current that flows along the edge of the PAH, and the middle ring current of PAHs having an odd number of benzene rings such as anthracene. In the present QOC treatment, the best target wavefunction for generation of the ring current through a designated path is determined by a Lagrange multiplier method. The target function is integrated into the ordinary QOC theory. To demonstrate the applicability of the QOC procedure, we took naphthalene and anthracene as the simplest examples of linear PAHs. The mechanisms of ring current generation were clarified by analyzing the temporal evolutions of the electronic excited states after coherent excitation by UV pulses or (UV+IR) pulses as well as those of electric fields of the optimal laser pulses. Time-dependent simulations of the perimeter ring current and middle ring current of anthracene, which are induced by analytical electric fields of UV pulsed lasers, were performed to reproduce the QOC results.

Quantum Design of π-Electron Ring Currents in Polycyclic Aromatic Hydrocarbons: Parallel and Antiparallel Ring Currents in Naphthalene.

Control of π-electrons in polycyclic aromatic hydrocarbons (PAHs) is one of the fundamental issues in optoelectronics for ultrafast optical switching devices. We have proposed an effective scenario for design of the generation of coherent ring currents in naphthalene (D2h), which is the smallest unit of planar PAHs. It has been demonstrated by using quantum chemical calculations and quantum optimal control (QOC) simulations that two types of ring currents, parallel and antiparallel, can be generated by resonance excitations by two linearly polarized lasers. A parallel (antiparallel) ring current means that the currents of two benzene rings run in the same (opposite) directions. The two types of ring currents may be experimentally identified by magnetic force microscopy. The QOC simulations indicate that a parallel ring current can be generated by using continuous wave and Gaussian pulse lasers with their time delay without relying on a sophisticated experimental apparatus. The present results provide a guiding principle of coherent π-electronics in PAHs for next-generation organic optical switching devices.

Induction of unidirectional π-electron rotations in low-symmetry aromatic ring molecules using two linearly polarized stationary lasers.

A new laser-control scenario of unidirectional π-electron rotations in a low-symmetry aromatic ring molecule having no degenerate excited states is proposed. This scenario is based on dynamic Stark shifts of two relevant excited states using two linearly polarized stationary lasers. Each laser is set to selectively interact with one of the two electronic states, the lower and higher excited states are shifted up and down with the same rate, respectively, and the two excited states become degenerate at their midpoint. One of the four control parameters of the two lasers, i.e. two frequencies and two intensities, determines the values of all the other parameters. The direction of π-electron rotations, clockwise or counter-clockwise rotation, depends on the sign of the relative phase of the two lasers at the initial time. An analytical expression for the time-dependent expectation value of the rotational angular momentum operator is derived using the rotating wave approximation (RWA). The control scenario depends on the initial condition of the electronic states. The control scenario with the ground state as the initial condition was applied to toluene molecules. The derived time-dependent angular momentum consists of a train of unidirectional angular momentum pulses. The validity of the RWA was checked by numerically solving the time-dependent Schrödinger equation. The simulation results suggest an experimental realization of the induction of unidirectional π-electron rotations in low-symmetry aromatic ring molecules without using any intricate quantum-optimal control procedure. This may open up an effective generation method of ring currents and current-induced magnetic fields in biomolecules such as amino acids having aromatic ring molecules for searching their interactions.

The generation of stationary π-electron rotations in chiral aromatic ring molecules possessing non-degenerate excited states.

The electron angular momentum is a fundamental quantity of high-symmetry aromatic ring molecules and finds many applications in chemistry such as molecular spectroscopy. The stationary angular momentum or unidirectional rotation of π electrons is generated by the excitation of a degenerated electronic excited state by a circularly-polarized photon. For low-symmetry aromatic ring molecules having non-degenerate states, such as chiral aromatic ring molecules, on the other hand, whether stationary angular momentum can be generated or not is uncertain and has not been clarified so far. We have found by both theoretical treatments and quantum optimal control (QOC) simulations that a stationary angular momentum can be generated even from a low-symmetry aromatic ring molecule. The generation mechanism can be explained in terms of the creation of a dressed-state, and the maximum angular momentum is generated by the dressed state with an equal contribution from the relevant two excited states in a simple three-electronic state model. The dressed state is formed by inducing selective nonresonant transitions between the ground and each excited state by two lasers with the same frequency but having different polarization directions. The selective excitation can be carried out by arranging each photon-polarization vector orthogonal to the electronic transition moment of the other transition. We have successfully analyzed the results of the QOC simulations of (P)-2,2'-biphenol of axial chirality in terms of the analytically determined optimal laser fields. The present findings may open up new types of chemical dynamics and spectroscopy by utilizing strong stationary ring currents and current-induced magnetic fields, which are created at a local site of large compounds such as biomolecules.

Ab initio quantum dynamical analysis of ultrafast nonradiative transitions via conical intersections in pyrazine.

We theoretically investigated the mechanism of ultrafast nonradiative transition through conical intersections in photoexcited pyrazine by ab initio quantum dynamical calculations. This work was motivated by the recent theoretical and experimental studies that presented conflicting results: the former is the on-the-fly semiclassical surface hopping calculation combined with the time-dependent density functional theory, which showed that nonadiabatic transitions from the optically bright S2 ((1)B(2u), ππ*) state to the optically dark S3 ((1)A(u), nπ*) and S4 ((1)B(2g), nπ*) states take place predominantly at the initial stage of electronic relaxation [U. Werner et al., Chem. Phys., 2008, 349, 319]; the latter is the pump-probe photoelectron spectroscopic measurement, which reported the S2 lifetime (22 ± 3 fs) of nonradiative decay to the almost dark S1 ((1)B(3u), nπ*) state [Y.-I. Suzuki et al., J. Chem. Phys., 2010, 132, 174302]. We constructed adiabatic and diabatic potential energy surfaces of these ππ* and nπ* states using the multireference configuration interaction method and calculated their diabatic couplings within two-dimensional subspaces spanned by selected ground-state normal coordinates. Contrary to the surface hopping study, our nuclear wave packet simulations demonstrated that nonadiabatic transitions to the S3 and S4 states are so small that the conventional two-state (S1 and S2) picture is valid. Ultrafast internal conversion of pyrazine, which is deemed to proceed with a 22 fs lifetime, in fact consists of three consecutive steps: (i) the wave packet excited to the S2 state travels toward the S2-S1 conical intersection in 10 fs, (ii) the nonadiabatic transition to the S1 state progresses at a rapid rate corresponding to a transient lifetime of 7 fs, and (iii) intramolecular vibrational energy redistribution occurs in the S1 state in about 80 fs after optical excitation. To verify this prediction, time-resolved experiments with a resolution of several fs or shorter are desirable.

Quantum Localization of Coherent π-Electron Angular Momentum in (P)-2,2'-Biphenol.

Controlling π-electrons with delocalized character is one of the fundamental issues in femtosecond and attosecond chemistry. Localization of π-electron rotation by using laser pulses is expected to play an essential role in nanoscience. The π-electron rotation created at a selected aromatic ring of a single molecule induces a local intense electromagnetic field, which is a new type of ultrafast optical control functioning. We propose a quantum localization of coherent π-electron angular momentum in (P)-2,2'-biphenol, which is a simple, covalently linked chiral aromatic ring chain molecule. The localization considered here consists of sequential two steps: the first step is to localize the π-electron angular momentum at a selected ring of the two benzene rings, and the other is to maintain the localization. Optimal control theory was used for obtaining the optimized electric fields of linearly polarized laser pulses to realize the localization. The optimal electric fields and the resultant coherent electronic dynamics are analyzed.

Neutral-fragmentation paths of methane induced by intense ultrashort IR laser pulses: ab initio molecular orbital approach.

Instantaneous (laser-field-dependent) potential energy curves leading to neutral fragmentations of methane were calculated at several laser intensities from 1.4 × 10(13) to 1.2 × 10(14) W/cm(2) (from 1.0 × 10(10) to 3.0 × 10(10) V/m) using ab initio molecular orbital (MO) methods to validate the observation of neutral fragmentations induced by intense femtosecond IR pulses (Kong et al. J. Chem. Phys. 2006, 125, 133320). Two fragmentation paths, CH(2) + 2H and CH(2) + H(2), in (1)T(2) superexcited states that are located in the energy range of 12-16 eV were considered as the reaction paths because these states are responsible for Jahn-Teller distortion opening up reaction paths during ultrashort pulses. As field intensity increased, the low-lying excited (1)A(1) states originated from the Jahn-Teller (1)T(2) states were substantially stabilized along the neutral-fragment path CH(4) → CH(2) + 2H and were located below the ionization threshold. On the other hand, the low-lying excited (1)B(1) states, which also originate from the Jahn-Teller (1)T(2) states, were embedded on the ionized state along the dissociation path to CH(2) + H(2). This indicates that ionic fragments, rather than neutral ones, are produced along the CH(2) + H(2) path. The computational results support neutral fragmentations through superexcited states proposed by Kong et al.

Quantum switching of π-electron rotations in a nonplanar chiral molecule by using linearly polarized UV laser pulses.

Nonplanar chiral aromatic molecules are candidates for use as building blocks of multidimensional switching devices because the π electrons can generate ring currents with a variety of directions. We employed (P)-2,2'-biphenol because four patterns of π-electron rotations along the two phenol rings are possible and theoretically determine how quantum switching of the π-electron rotations can be realized. We found that each rotational pattern can be driven by a coherent excitation of two electronic states under two conditions: one is the symmetry of the electronic states and the other is their relative phase. On the basis of the results of quantum dynamics simulations, we propose a quantum control method for sequential switching among the four rotational patterns that can be performed by using ultrashort overlapped pump and dump pulses with properly selected relative phases and photon polarization directions. The results serve as a theoretical basis for the design of confined ultrafast switching of ring currents of nonplanar molecules and further current-induced magnetic fluxes of more sophisticated systems.

Laser-polarization effects on coherent vibronic excitation of molecules with quasi-degenerate electronic states.

The laser-polarization effects on nonadiabatically coupled π-electron rotation (ring current) and molecular vibration have been theoretically analyzed for aromatic molecules with quasi-degenerate excited states irradiated by an ultrashort laser pulse of arbitrary polarization. We first derived general formulations of the coherent electronic wave packet and expectation value of electronic angular momentum within a frozen-nuclei model. The relative quantum phase of the superposed quasi-degenerate states, which determines the oscillating behavior of angular momentum, can be manipulated by the ellipticity and orientation of the incident laser. Nuclear wave packet simulations with a model molecule confirmed the controllability of π-electron rotation, although the angular momentum is gradually reduced by nonadiabatic couplings. The amplitude of molecular vibration depends prominently on the orientation of linear polarization vectors rather than the helicity of circular polarization. The characteristic feature in vibrational amplitudes is attributed to the interference in nonadiabatic transition governed by the relative quantum phase between nuclear wave packets. This offers a new strategy for laser control of molecular vibrations through the wave packet interference in nonadiabatic transition.

Bmi1 regulates cell fate via tumor suppressor WWOX repression in small-cell lung cancer cells.

Mortality from lung cancer is important worldwide. Recently, epigenetic aberration of lung cancer, not only genomic DNA methylation but also chromatin modification, has become an important target for lung cancer research, although previous research has demonstrated that lung cancer develops as a result of both environmental and genetic factors. Here, we demonstrated that an epigenetic regulator/polycomb group protein Bmi1 is more highly expressed in small-cell lung cancer (SCLC) than in non-small-cell lung cancer by immunohistochemical analysis. In vitro experiments indicated that Bmi1 reduction by lentivirus-derived shRNA significantly suppressed proliferation, colony formation and in vivo tumor formation. Importantly, apoptosis was induced by Bmi1 depletion in small-cell lung cancer cells. Furthermore, a tumor suppressor WWOX was identified as a Bmi1 target in the cells by a chromatin immunoprecipitation assay and a quantitative real-time PCR assay; WWOX had a role as a tumor suppressor in SCLC cells; therefore, the Bmi1/WWOX pathway could be a new candidate for a new therapeutic approach for SCLC.

Shape anisotropy induces rotations in optically trapped red blood cells.

A combined experimental and theoretical study is carried out to probe the rotational behavior of red blood cells (RBCs) in a single beam optical trap. We induce shape changes in RBCs by altering the properties of the suspension medium in which live cells float. We find that certain shape anisotropies result in the rotation of optically trapped cells. Indeed, even normal (healthy) RBCs can be made to rotate using linearly polarized trapping light by altering the osmotic stress the cells are subjected to. Hyperosmotic stress is found to induce shape anisotropies. We also probe the effect of the medium's viscosity on cell rotation. The observed rotations are modeled using a Langevin-type equation of motion that takes into account frictional forces that are generated as RBCs rotate in the medium. We observe good correlation between our measured data and calculated results.

Ultrafast radiationless transition pathways through conical intersections in photo-excited 9H-adenine.

We performed CASSCF and MRCI calculations for determination of the effective pathways of ultrafast radiationless transitions from the optically allowed ππ* 1La state to the ground state S0 of 9H-adenine. The nπ*, πσ*, and two ππ* states were taken into account as states involved in the radiationless process. Optimized geometry and conical intersections were searched in the full dimensional space for the vibrational degrees of freedom by using the suite of quantum chemistry codes MOLPRO. The MRCI transition energies to excited states are in good agreement with the experimental values. The mechanisms of three competing pathways, two indirect pathways via the πσ* and nπ* states, 1La→πσ*→S0 and 1La→nπ*→ S0, and a direct pathway 1La→S0, were examined on the basis of the structures and energies of conical intersections involved in ultrafast radiationless transitions from 1La to S0. Any conical intersection between the πσ* and nπ* states was not found. This suggests that the two indirect pathways are independent of each other. The ππ* 1La-πσ* conical intersection lies higher than the ππ* 1La state at the Franck-Condon geometry by 0.19 eV according to the present MRCI calculation, which is consistent with the experimental observation that a new channel is open at the excess energy of 0.2 eV above the band origin of the ππ* 1La state. It is concluded that relaxation from the ππ* 1La-πσ* conical intersection to S0 occurs mainly through the πσ*-S0 conical intersection. The ππ* 1La-nπ* conical intersection lies higher by 0.1 eV (MRCI value) than the ππ* 1La state at the Franck-Condon geometry. The fast decay component in time-resolved spectra of 9H-adenine is attributed to rapid radiationless transitions to the nπ* state via this conical intersection followed by the transition to S0 via the nπ*-S0 (or ππ* 1La-S0) conical intersection. The ππ* 1La-S0 conical intersection of large out-of-plane distortion has the lowest energy among the conical intersections found in this study. We identified the transition state between the ππ* 1La at the Franck-Condon geometry and the ππ* 1La-S0 conical intersection. The MRCI energy of the transition state on the 1La potential surface is higher by 0.21 eV than the vertical excitation energy. The possibility of strong coupling between the two close-lying states 1La and nπ* indicates that, besides this direct pathway, radiationless transitions to S0 via the ππ* 1La-S0 conical intersection can also occur after rapid relaxations between 1La and nπ*. The analysis of the h-vector for each conical intersection has shown that the active coupling for the πσ* pathway is dominated by the out-of-plane normal mode ν10, while the active coupling for the nπ* pathway is distributed among many normal modes. Control of the branching ratio of the two indirect pathways can be achieved by selective excitation of single vibronic levels involving active coupling modes such as the mode ν10.

Nonadiabatic response model of laser-induced ultrafast pi-electron rotations in chiral aromatic molecules.

We theoretically investigated the nonadiabatic couplings between optically induced pi-electron rotations and molecular vibrations in a chiral aromatic molecule irradiated by a nonhelical, linearly polarized laser pulse. The results of wave packet dynamics simulation show that the vibrational amplitudes strongly depend on the initial rotation direction, clockwise or counterclockwise, which is controlled by the polarization direction of the incident pulse. This suggests that attosecond pi-electron rotations can be observed by spectroscopic detection of femtosecond molecular vibrations.

Spin-orbit coupling effects in dihydrides of third-row transition elements. II. Interplay of nonadiabatic coupling in the dissociation path of rhenium dihydride.

This is the second paper in a series of investigations on spin-orbit coupling (SOC) effects in dihydrides of third-row transition elements. The dissociation path of rhenium dihydride was explored using the multiconfiguration self-consistent-field method followed by diagonalization of SOC matrices, in which the Stevens-Basch-Krauss-Jasien-Cundari (SBKJC) basis sets were employed after adding one set of polarization functions for each atom. The most stable rhenium dihydride has a linear structure and its ground state is (6)Sigma(g)(+). Both C(2v) and C(s) dissociation paths into a Re atom and a hydrogen molecule (Re((6)S) + H(2)((1)Sigma(g)(+))) were explored on the potential energy curves of low-lying states. A relatively high energy barrier was obtained along the C(2v) path and two conical intersections were found at the H-Re-H angles of 29.8 degrees and 96.1 degrees along the C(2v) path. Since it was revealed that the geometrical deformation to C(s) symmetry at the H-Re-H angle of 29.8 degrees does not provide explicit lowering of the energy barrier for the dissociation, even after considering nonadiabatic couplings (NACs) in the neighborhood of the conical intersections, it can be concluded that the most feasible path is hopping from the lowest (6)A(1) state to the lowest (6)B(2) state at the H-Re-H angle of 96.1 degrees followed by hopping from the lowest (6)B(2) state back to the lowest (6)A(1) state at the H-Re-H angle of 29.8 degrees, where the latter crossing point is the highest in energy along this path. Thus, when the molecular system can reach the areas of these crossing points, the molecular system hops from one of the states to another owing to NAC or SOC effects; especially, SOC effects become important at the crossing point with C(2v) symmetry.

Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B.

Cell lineages generated during development and tissue maintenance are derived from self-renewing stem cells by differentiation of their committed progeny. Recent studies suggest that epigenetic mechanisms, and in particular the Polycomb group (PcG) of genes, play important roles in controlling stem cell self-renewal. Here, we address PcG regulation of stem cell self-renewal and differentiation through inactivation of Ring1B, a histone H2A E3 monoubiquitin ligase, in embryonic neural stem cells (NSCs) from the olfactory bulb of a conditional mouse mutant line. We show that neural stem/progenitor cell proliferation in vivo and in neurosphere assays is impaired, lacking Ring1B, and their self-renewal and multipotential abilities, assessed as sphere formation and differentiation from single cells, are severely affected. We also observed unscheduled neuronal, but not glial, differentiation of mutant stem/progenitor cells under proliferating conditions, an alteration enhanced in cells also lacking Ring1A, the Ring1B paralog, some of which turned into morphologically identifiable neurons. mRNA analysis of mutant cells showed upregulation of some neuronal differentiation-related transcription factors and the cell proliferation inhibitor Cdkn1a/p21, as well as downregulation of effectors of the Notch signaling pathway, a known inhibitor of neuronal differentiation of stem/progenitor cells. In addition, differentiation studies of Ring1B-deficient progenitors showed decreased oligodendrocyte formation in vitro and enhanced neurogenesis and reduced gliogenesis in vivo. These data suggest a role for Ring1B in maintenance of the undifferentiated state of embryonic neural stem/progenitor cells. They also suggest that Ring1B may modulate the differentiation potential of NSCs to neurons and glia.

Sall4 is essential for stabilization, but not for pluripotency, of embryonic stem cells by repressing aberrant trophectoderm gene expression.

Sall4 is a mouse homolog of a causative gene of the autosomal dominant disorder Okihiro syndrome. We previously showed that the absence of Sall4 leads to lethality during peri-implantation and that Sall4-null embryonic stem (ES) cells proliferate poorly with intact pluripotency when cultured on feeder cells. Here, we report that, in the absence of feeder cells, Sall4-null ES cells express the trophectoderm marker Cdx2, but are maintained for a long period in an undifferentiated state with minimally affected Oct3/4 expression. Feeder-free Sall4-null ES cells contribute solely to the inner cell mass and epiblast in vivo, indicating that these cells still retain pluripotency and do not fully commit to the trophectoderm. These phenotypes could arise from derepression of the Cdx2 promoter, which is normally suppressed by Sall4 and the Mi2/NuRD HDAC complex. However, proliferation was impaired and G1 phase prolonged in the absence of Sall4, suggesting another role for Sall4 in cell cycle control. Although Sall1, also a Sall family gene, is known to genetically interact with Sall4 in vivo, Sall1-null ES cells have no apparent defects and no exacerbation is observed in ES cells lacking both Sall1 and Sall4, compared with Sall4-null cells. This suggests a unique role for Sall4 in ES cells. Thus, though Sall4 does not contribute to the central machinery of the pluripotency, it stabilizes ES cells by repressing aberrant trophectoderm gene expression.