Project description:Idiopathic pulmonary fibrosis (IPF) is a common form of interstitial lung disease (ILD) resulting in alveolar remodeling and progressive loss of pulmonary function due to chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts.
Project description:Gene expression profiles among avascular region (around ventricular zone), highly vascularized region with honeycomb-patterned vascular plexus (around subventricular zone and intermediate zone), and cortical plate with vertically oriented vessels from laser-captured microdissected E14.5 neocortex were compared by microarray
Project description:To characterize female aged Efemp1 R345W knock-in (Efemp1ki/ki) mice, a model for Doyne honeycomb retinal dystrophy/malattia leventinese by bulk RNA sequencing We performed differential expression and gene set enrichment analysis analysis using data obtained from RNA-seq of the neural retina and posterior eyecups (whole eye without lens and retina) from 3- to 17-month-old Efemp1+/+ and Efemp1ki/ki mice
Project description:This dataset represent supplemental data for publication submitted to Human Molecular Genetics in 2022. Briefly, Efemp1 R345W is a protein misfolding-prone mutation in humans causing Doyne honeycomb retinal dystrophy/Mallatia Leventinese (DHRD/ML), a disease sharing similar clinical pathology with age-related macular degeneration (AMD). Efemp1R345W/R345W knock-in mice (Efemp1ki/ki mice) develop deposits on the basal side of retinal pigment epithelial (RPE) cells, which is complement C3- dependent. We assessed alternative complement pathway component factor B (Cfb) in sub-RPE deposit formation in Efemp1ki/ki mice.
Project description:Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to phenotypic diversity, its interaction with genetic variation requires further investigation. MethylC-seq from naturally-occurring Arabidopsis accessions
Project description:Interventions: different phenotypes vs. HNPCC group vs. healthy control group:Nil
Primary outcome(s): Alpha diversity analysis;ß-diversity analysis;LDA EffectSize (LEfSe) analysis
Study Design: Factorial
Project description:Opioids such as morphine have many beneficial properties as analgesics, however, opioids may induce multiple adverse gastrointestinal symptoms. We have recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. However, it is unclear how opioids modulate the gut homeostasis. By using a mouse model of morphine treatment, we studied effects of morphine treatment on gut microbiome. We characterized phylogenetic profiles of gut microbes, and found a significant shift in the gut microbiome and increase of pathogenic bacteria following morphine treatment when compared to placebo. In the present study, wild type mice (C57BL/6J) were implanted with placebo, morphine pellets subcutaneously. Fecal matter were taken for bacterial 16s rDNA sequencing analysis at day 3 post treatment. A scatter plot based on an unweighted UniFrac distance matrics obtained from the sequences at OTU level with 97% similarity showed a distinct clustering of the community composition between the morphine and placebo treated groups. By using the chao1 index to evaluate alpha diversity (that is diversity within a group) and using unweighted UniFrac distance to evaluate beta diversity (that is diversity between groups, comparing microbial community based on compositional structures), we found that morphine treatment results in a significant decrease in alpha diversity and shift in fecal microbiome at day 3 post treatment compared to placebo treatment. Taxonomical analysis showed that morphine treatment results in a significant increase of potential pathogenic bacteria. Our study shed light on effects of morphine on the gut microbiome, and its role in the gut homeostasis.
