Aneuploid embryonic stem cells drive teratoma metastasis.

Aneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities for migration and organ colonization. Single-cell RNA sequencing of aneuploid primary teratomas and metastases identified a unique cell population with high stemness that was absent in diploid ESCs-derived teratomas. Further investigation revealed that aneuploid cells displayed decreased proteasome activity and overactivated endoplasmic reticulum (ER) stress during differentiation, thereby restricting the degradation of proteins produced from extra chromosomes in the ESC state and causing differentiation deficiencies. Noticeably, both proteasome activator Oleuropein and ER stress inhibitor 4-PBA can effectively inhibit aneuploid teratoma metastasis.

[Generation of skin-derived iPSCs from an Osteogenesis imperfecta patient carrying WNT1c.677C>T mutation].

OBJECTIVE: To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI. METHODS: The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay. RESULTS: The patient was found to carry homozygous missense c.677C>T (p.Ser226Leu) mutation of the WNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46,XX). CONCLUSION: A patient-specific WNT1 gene mutation (WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.

FLT3LG and IFITM3P6 consolidate T cell activity in the bone marrow microenvironment and are prognostic factors in acute myelocytic leukemia.

Acute myelocytic leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage. CD4+ and CD8+ T cells play pivotal roles in influencing AML progression but are functionally suppressed in the bone marrow microenvironment. We aimed to find hub genes related to T cell exhaustion and suppression, thereby providing evidence for immunotherapy. In this study, gene transcriptome expression data from TCGA and TARGET databases were utilized to find key genes. Firstly, CIBERSORT immune cell infiltration algorithm and WGCNA method were used to identify CD4+ and CD8+ T cells-related genes. Univariate and multivariate cox regression analyses were then introduced to construct the overall survival prognosis model and included hub genes. The ESTIMATE and ssGSEA scoring methods were used to analyze the correlation between the hub genes and immune activity. Single-cell transcriptome analysis was applied to detect the immune cells expressing hub genes, hence, to detect exact mechanisms. Consequently, FLT3LG and IFITM3P6 were determined to be positively correlated with patients' overall survival and microenvironment immune activity. Further study suggested FLT3-FLT3LG and IFITM3P6-miR-6748-3p-CBX7 signaling axes were involved in CD4+ and CD8+ T cells activation. This may be one of the mechanisms of T cells suppression in AML.

Corrigendum: Understanding Thermostability Factors of Barley Limit Dextrinase by Molecular Dynamics Simulations.

[This corrects the article DOI: 10.3389/fmolb.2020.00051.].

Understanding Thermostability Factors of Barley Limit Dextrinase by Molecular Dynamics Simulations.

Limit dextrinase (LD) is the only endogenous starch-debranching enzyme in barley (Hordeum vulgare, Hv), which is the key factor affecting the production of a high degree of fermentation. Free LD will lose its activity in the mashing process at high temperature in beer production. However, there remains a lack of understanding on the factor affecting the themostability of HvLD at the atomic level. In this work, the molecular dynamics simulations were carried out for HvLD to explore the key factors affecting the thermal stability of LD. The higher value of root mean square deviation (RMSD), radius of gyration (R g), and surface accessibility (SASA) suggests the instability of HvLD at high temperatures. Intra-protein hydrogen bonds and hydrogen bonds between protein and water decrease at high temperature. Long-lived hydrogen bonds, salt bridges, and hydrophobic contacts are lost at high temperature. The salt bridge interaction analysis suggests that these salt bridges are important for the thermostability of HvLD, including E568-R875, D317-R378, D803-R884, D457-R214, D468-R395, D456-R452, D399-R471, and D541-R542. Root mean square fluctuation (RMSF) analysis identified the thermal-sensitive regions of HvLD, which will facilitate enzyme engineering of HvLD for enhanced themostability.

Incorporation of Cesium Ions into MA1- xCs xPbI3 Single Crystals: Crystal Growth, Enhancement of Stability, and Optoelectronic Properties.

Organic-inorganic hybrid methylammonium lead iodide perovskite (MAPbI3) has attracted extensive attention in a series of optoelectronic devices. The photoelectric properties of the MAPbI3 single crystal have been revealed to be much better than those of it polycrystalline counterparts. However, its poor moisture and heat resistance severely limited further development. The introduction of Cs+ into polycrystalline films has shown to be an effective way to enhance its moisture resistance through a passivation effect. However, the entrance abilities of Cs+ into a MAPbI3 crystal lattice and the influence on photoelectric properties of a single crystal were not clear until now. Therefore, we attempted to grow large MA1- xCs xPbI3 single crystals to introduce Cs+ into the crystal lattice. The existence of Cs+ brought lattice shrinkage and enhanced stability of the MAPbI3 single crystal. A moderate quantity of Cs+ (2%) proved to heighten the photoelectric properties, whereas an excess quantity of Cs+ (5%) brought more shallow defects, which ultimately deteriorated the photoelectric properties.

Design Growth of MAPbI3 Single Crystal with (220) Facets Exposed and Its Superior Optoelectronic Properties.

MAPbI3 is deemed as the most prominent member in hybrid perovskites family because of its extremely optoelectronic properties. However, some issues and puzzles are still in expectation of their answers, such as stabilities, hysteresis, ferroelectricity, and so on. To bridge the distinctions between MAPbI3 single crystal and thin films, large-size single crystals are demanded. On the contrary, crystal structure anisotropy-dependent optoelectronic properties is an inevitable topic. A series of large-size MAPbI3 single crystals with (220) facets exposed were successfully grown, using high concentration solutions and large-size seed crystals to match growth rates of (100) and (220) facets. The optoelectronic properties of photocurrents, responsivity, EQE, and detectivity clearly showed significant anisotropy of optoelectronic properties in MAPbI3 single crystal. According to ion migration theory, the anisotropy of optoelectronic properties was interpreted. We hope this result will be helpful to guide oriented growth MAPbI3 thin films.

Polarization-Dependent Optoelectronic Performances in Hybrid Halide Perovskite MAPbX3 (X = Br, Cl) Single-Crystal Photodetectors.

Hybrid organic-inorganic lead halide perovskites (HOIPs) have received significant attention because of their impressive performances in the fields of solar cells and photoelectric detection. In the past five years, great efforts have been made to improve the crystallinity, reduce grain boundaries, and enhance the stabilities of perovskite films. Compared with films, HOIP single crystals possess fewer grain boundaries and stronger optoelectronic properties and can be applied in optoelectronic devices. As the most popular HOIP member, single crystals of MAPbX3 (X = Br, Cl) are deemed as important candidates for ultraviolet-visible photodetectors, in which the crystal structure anisotropy largely affects the detection performance. In this study, high-quality cubic single crystals of MAPbBr3 and MAPbCl3 were successfully grown from solutions. Taking advantages of their smooth (100) facets, planar metal-semiconductor-metal photodetectors were fabricated using Au interdigitated electrodes. The optoelectronic performances under nonpolarized and linearly polarized lights were explored. The optoelectronic performances were dependent on linearly polarized lights. Interestingly, both responsivity and external quantum efficiency were greatly enhanced under the excitation with linearly polarized lights. Moreover, the polarization-related optical absorptions and the electron densities within the (100) plane could be used to interpret different optoelectronic performances of single crystals of MAPbX3 (X = Br, Cl) under various linearly polarized lights.

Enhanced Optoelectronic Performance on the (110) Lattice Plane of an MAPbBr3 Single Crystal.

Hybrid organic-inorganic lead halide perovskites have attracted significant attention due to their impressive optoelectronic properties. MAPbX3 (MA= CH3NH3+, X= Cl, Br or I), the most popular member of this family, has been recognized as an important next-generation optoelectronic materials contender, and remarkable progress has been achieved in both thin films and single crystals. However, the lack of optimizations in energy harvest, transportation, carrier extraction, and process compatibility is hindering their future development. In this study, a triangle prism MAPbBr3 single crystal exposing (100) and (110) crystallographic planes was successfully synthesized, and the optoelectronic performances of these two lattice planes were systematically explored by employing a planar metal-semiconductor-metal (MSM) device. Compared to the device fabricated on the (100) plane, a 153.33% enhancement of responsivity was achieved under 10 µW irradiation and 10 V bias on the (110) plane. Finally, possible mechanism for such an enhancement was discussed based on the different defect migration behaviors of (100) and (110) planes.