Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro. Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

No abstract

RNA-sequencing (RNA-seq) can generate millions of reads to provide clues for analyzing novel or abnormal alternative splicing (AS) events in cells. However, current methods for exploring AS events are still far from being satisfactory. Here, we present Comprehensive AS Hunting (CASH), which constructs comprehensive splice sites including known and novel AS sites in cells, and identifies differentially AS events between cells. We illuminated the versatility of CASH on RNA-seq data from a wide range of species and also on simulated in silico data, validated the advantages of CASH over other AS predictors and exhibited novel differentially AS events. Moreover, we used CASH to identify SRSF10-regulated AS events and investigated the evolution of SRSF10-regulated splicing. The results showed that SRSF10-regulated splicing events are highly evolvable from chickens, mice to humans. However, SRSF10-regulated splicing model was observed to be immutable, in which SRSF10 binding to cassette exon promotes exon inclusion while binding to downstream exon induces exon skipping. Altogether, CASH can significantly improve the detection of AS events and facilitate the study of AS regulation and function in cells; the SRSF10 data first demonstrate a flexibility of SRSF10 with their regulated splicing events but an immutability of SRSF10-regulated splicing model to produce opposite AS outcomes in vertebrates.

No abstract

Apolipoprotein A-I (apoA-I) is an important component of highdensity lipoprotein particles that mediates reverse cholesterol transport out of cells by interacting with the ATP-binding cassette transporter 1 (ABCA1). apoA-I has also been shown to attenuate neutrophilic airway inflammation in experimental ovalbumin (OVA)-induced asthma by reducing the expression of granulocyte colony-stimulating factor (G-CSF). Here, we hypothesized that overexpression of the ABCA1 transporter might similarly attenuate OVA-induced neutrophilic airway inflammation. Tie2-human ABCA1 (hABCA1) mice expressing human ABCA1 under the control of the Tie2 promoter, which is primarily expressed by vascular endothelial cells, but can also be expressed by macrophages, received daily intranasal OVA challenges, 5 d/wk for 5 weeks. OVAchallenged Tie2-hABCA1 mice had significant reductions in total bronchoalveolar lavage fluid (BALF) cells that reflected a decrease in neutrophils, as well as reductions in peribronchial inflammation, OVA-specific IgE levels, and airway epithelial thickness. The reduced airway neutrophilia in OVA-challenged Tie2-hABCA1 mice was associated with significant decreases in G-CSF protein levels in pulmonary vascular endothelial cells, alveolar macrophages, and BALF. Intranasal administration of recombinant murine G-CSF to OVA-challenged Tie2-hABCA1 mice for 5 days increased BALF neutrophils to a level comparable to that of OVA-challenged wildtype mice. We conclude that ABCA1 suppresses OVA-induced airway neutrophilia by reducing G-CSF production by vascular endothelial cells and alveolar macrophages. These findings suggest that ABCA1 expressed by vascular endothelial cells and alveolar macrophages may play important roles in attenuating the severity of neutrophilic airway inflammation in asthma.