Manganese therapy for dyslipidemia and plaque reversal in murine models

Precise control of circulating lipid levels is vital in both health and disease.We recently uncovered that bulk lipids,transported by lipoproteins,enter the circulation initially via the coat protein complex II(COPII)in a condensation-dependent manner.Divalent manganese,acting as a signaling messenger,selectively controls COPII condensation to regulate lipid homeostasis in vivo.Here,we present evidence for a manganese-based therapy in murine models of hypolipidemia and hyperlipidemia.

De?ning gene networks controlling the maintenance and function of the differentiation niche by an in vivo systematic RNAi screen

In the Drosophila ovary, escort cells (ECs) extrinsically control germline stem cell (GSC) maintenance and progeny differentiation. However, the underlying mechanisms remain poorly understood. In this study,we identified 173 EC genes for their roles in controlling GSC maintenance and progeny differentiation by using an in vivo systematic RNAi approach. Of the identified genes, 10 and 163 are required in ECs to promote GSC maintenance and progeny differentiation, respectively. The genes required for progeny differentiation fall into different functional categories, including transcription, mRNA splicing, protein degradation, signal transduction and cytoskeleton regulation. In addition, the GSC progeny differentiation defects caused by defective ECs are often associated with BMP signaling elevation, indicating that preventing BMP signaling is a general functional feature of the differentiation niche. Lastly, exon junction complex (EJC) components, which are essential for mRNA splicing, are required in ECs to promote GSC progeny differentiation by maintaining ECs and preventing BMP signaling. Therefore, this study has identified the major regulators of the differentiation niche, which provides important insights into how stem cell progeny differentiation is extrinsically controlled.