In vivo manipulation of the extracellular matrix induces vascular regression in a basal chordate.

We investigated the physical role of the extracellular matrix (ECM) in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent, extracorporeal vascular network encompassing an area >100 cm2 We found that the collagen cross-linking enzyme lysyl oxidase is expressed in all vascular cells and that in vivo inhibition using β-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 h. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose dependent. Pharmacological inhibition of both focal adhesion kinase (FAK) and Raf also induced regression, and levels of phosphorylated FAK in vascular cells decreased during BAPN treatment and FAK inhibition but not Raf inhibition, suggesting that physical changes in the vessel ECM are detected via canonical integrin signaling pathways. Regression is driven by apoptosis and extrusion of cells through the basal lamina, which are then engulfed by blood-borne phagocytes. Extrusion and regression occurred in a coordinated manner that maintained vessel integrity, with no loss of barrier function. This suggests the presence of regulatory mechanisms linking physical changes to a homeostatic, tissue-level response

Wnt affects symmetry and morphogenesis during post-embryonic development in colonial chordates

International audienceBackground : Wnt signaling is one of the earliest and most highly conserved regulatory pathways for the establishment of the body axes during regeneration and early development. In regeneration, body axes determination occurs independently of tissue rearrangement and early developmental cues. Modulation of the Wnt signaling in either process has shown to result in unusual body axis phenotypes. Botryllus schlosseri is a colonial ascidian that can regenerate its entire body through asexual budding. This processes leads to an adult body via a stereotypical developmental pathway (called blastogenesis), without proceeding through any embryonic developmental stages.Results : In this study, we describe the role of the canonical Wnt pathway during the early stages of asexual development. We characterized expression of three Wnt ligands (Wnt2B, Wnt5A, and Wnt9A) by in situ hybridization and qRT-PCR. Chemical manipulation of the pathway resulted in atypical budding due to the duplication of the A/P axes, supernumerary budding, and loss of the overall cell apical-basal polarity.Conclusions : Our results suggest that Wnt signaling is used for equivalent developmental processes both during embryogenesis and asexual development in an adult organism, suggesting that patterning mechanisms driving morphogenesis are conserved, independent of embryonic, or regenerative development

In vivo manipulation of the extracellular matrix induces vascular regression in a basal chordate.

We investigated the physical role of the extracellular matrix (ECM) in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent, extracorporeal vascular network encompassing an area >100 cm2 We found that the collagen cross-linking enzyme lysyl oxidase is expressed in all vascular cells and that in vivo inhibition using β-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 h. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose dependent. Pharmacological inhibition of both focal adhesion kinase (FAK) and Raf also induced regression, and levels of phosphorylated FAK in vascular cells decreased during BAPN treatment and FAK inhibition but not Raf inhibition, suggesting that physical changes in the vessel ECM are detected via canonical integrin signaling pathways. Regression is driven by apoptosis and extrusion of cells through the basal lamina, which are then engulfed by blood-borne phagocytes. Extrusion and regression occurred in a coordinated manner that maintained vessel integrity, with no loss of barrier function. This suggests the presence of regulatory mechanisms linking physical changes to a homeostatic, tissue-level response

Image_1_Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.eps

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for InterpretationIncreased expression of cilia-related genes in clinically indistinguishable infants with critical RSV may differentiate between infants who will require prolonged hospitalization and infants who will recover quickly. Validation of these findings in a larger cohort is needed to determine whether a cilia-related gene signature can predict duration of illness in infants with critical bronchiolitis. The ability to identify which infants with critical RSV bronchiolitis may require prolonged hospitalization using non-invasive nasal samples would provide invaluable prognostic information to parents and medical providers.</p

Image_2_Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.eps

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for InterpretationIncreased expression of cilia-related genes in clinically indistinguishable infants with critical RSV may differentiate between infants who will require prolonged hospitalization and infants who will recover quickly. Validation of these findings in a larger cohort is needed to determine whether a cilia-related gene signature can predict duration of illness in infants with critical bronchiolitis. The ability to identify which infants with critical RSV bronchiolitis may require prolonged hospitalization using non-invasive nasal samples would provide invaluable prognostic information to parents and medical providers.</p

DataSheet_3_Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.xlsx

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for InterpretationIncreased expression of cilia-related genes in clinically indistinguishable infants with critical RSV may differentiate between infants who will require prolonged hospitalization and infants who will recover quickly. Validation of these findings in a larger cohort is needed to determine whether a cilia-related gene signature can predict duration of illness in infants with critical bronchiolitis. The ability to identify which infants with critical RSV bronchiolitis may require prolonged hospitalization using non-invasive nasal samples would provide invaluable prognostic information to parents and medical providers.</p

DataSheet_4_Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.xlsx

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for InterpretationIncreased expression of cilia-related genes in clinically indistinguishable infants with critical RSV may differentiate between infants who will require prolonged hospitalization and infants who will recover quickly. Validation of these findings in a larger cohort is needed to determine whether a cilia-related gene signature can predict duration of illness in infants with critical bronchiolitis. The ability to identify which infants with critical RSV bronchiolitis may require prolonged hospitalization using non-invasive nasal samples would provide invaluable prognostic information to parents and medical providers.</p

DataSheet_1_Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.xlsx

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for InterpretationIncreased expression of cilia-related genes in clinically indistinguishable infants with critical RSV may differentiate between infants who will require prolonged hospitalization and infants who will recover quickly. Validation of these findings in a larger cohort is needed to determine whether a cilia-related gene signature can predict duration of illness in infants with critical bronchiolitis. The ability to identify which infants with critical RSV bronchiolitis may require prolonged hospitalization using non-invasive nasal samples would provide invaluable prognostic information to parents and medical providers.</p

DataSheet_5_Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.xlsx

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for InterpretationIncreased expression of cilia-related genes in clinically indistinguishable infants with critical RSV may differentiate between infants who will require prolonged hospitalization and infants who will recover quickly. Validation of these findings in a larger cohort is needed to determine whether a cilia-related gene signature can predict duration of illness in infants with critical bronchiolitis. The ability to identify which infants with critical RSV bronchiolitis may require prolonged hospitalization using non-invasive nasal samples would provide invaluable prognostic information to parents and medical providers.</p