Engrafted glial progenitor cells yield long-term integration and sensory improvement in aged mice.

Aging causes astrocyte morphological degeneration and functional deficiency, which impairs neuronal functions. Until now, whether age-induced neuronal deficiency could be alleviated by engraftment of glial progenitor cell (GPC) derived astrocytes remained unknown. In the current study, GPCs were generated from embryonic cortical neural stem cells in vitro and transplanted into the brains of aged mice. Their integration and intervention effects in the aged brain were examined 12 months after transplantation. Results indicated that these in-vitro-generated GPC-derived astrocytes possessed normal functional properties. After transplantation they could migrate, differentiate, achieve long-term integration, and maintain much younger morphology in the aged brain. Additionally, these GPC-derived astrocytes established endfeet expressing aquaporin-4 (AQP4) and ameliorate AQP4 polarization in the aged neocortex. More importantly, age-dependent sensory response degeneration was reversed by GPC transplantation. This work demonstrates that rejuvenation of the astrocyte niche is a promising treatment to prevent age-induced degradation of neuronal and behavioral functions.

SOX2 modulated astrocytic process plasticity is involved in arsenic-induced metabolic disorders.

Metabolic disorders induced by arsenic exposure have attracted great public concern. However, it remains unclear whether hypothalamus-based central regulation mechanisms are involved in this process. Here, we exposed mice to 100 µg/L arsenic in drinking water and established a chronic arsenic exposure model. Our study revealed that chronic arsenic exposure caused metabolic disorders in mice including impaired glucose metabolism and decreased energy expenditure. Arsenic exposure also impaired glucose sensing and the activation of proopiomelanocortin (POMC) neurons in the hypothalamus. In particular, arsenic exposure damaged the plasticity of hypothalamic astrocytic process. Further research revealed that arsenic exposure inhibited the expression of sex-determining region Y-Box 2 (SOX2), which decreased the expression level of insulin receptors (INSRs) and the phosphorylation of AKT. The conditional deletion of astrocytic SOX2 exacerbated arsenic-induced effects on metabolic disorders, the impairment of hypothalamic astrocytic processes, and the inhibition of INSR/AKT signaling. Furthermore, the arsenic-induced impairment of astrocytic processes and inhibitory effects on INSR/AKT signaling were reversed by SOX2 overexpression in primary hypothalamic astrocytes. Together, we demonstrated here that chronic arsenic exposure caused metabolic disorders by impairing SOX2-modulated hypothalamic astrocytic process plasticity in mice. Our study provides evidence of novel central regulatory mechanisms underlying arsenic-induced metabolic disorders and emphasizes the crucial role of SOX2 in regulating the process plasticity of adult astrocytes.

Serratia marcescens-S3 inhibits Potato virus Y by activating ubiquitination of molecular chaperone proteins NbHsc70-2 in Nicotiana benthamiana.

The potato virus Y (PVY) is a plant virus that causes massive crop losses globally, especially in Solanaceae crops. A strain of the plant growth-promoting rhizobacterium (PGPR), Serratia marcescens-S3 was found to inhibit PVY replication in Nicotiana benthamiana. However, there have been no in-depth studies demonstrating the underlying mechanism. In the current study, we found that ubiquitination of NbHsc70-2 is an important way for Serratia marcescens-S3 to trigger induced systemic resistance (ISR). After the treatment with S. marcescens-S3, the protein level of NbHsc70-2 reduced significantly. Inhibiting of ubiquitination increased the accumulation of NbHsc70-2 in plants and reduced S. marcescens-S3-mediated resistance to PVY. Furthermore, transgenic engineered Nicotiana benthamiana NbHsc70-2KO and NbHsc70-2USM were constructed using CRISPR-Cas9-mediated NbHsc70-2 knock-out and ubiquitination respectively. S. marcescens-S3 significantly reduced the inhibition of NbHsc70-2 protein accumulation in NbHsc70-2KO and NbHsc70-2USM . The virulence of PVY was stronger in NbHsc70-2USM than the wild-type plants. These results showed that S. marcescens-S3 increases the ubiquitination of NbHsc70-2 to inhibit the recruitment of molecular chaperone NbHsc70-2 to reduce its replication and infection of PVY.