Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human NEK10 knockout airway ALI Fe-IMAC-MSMS

ABSTRACT: We identified inactivating mutations in NEK10, a poorly characterized human protein kinase, in a novel human bronchiectasis syndrome. In order to understand effects of loss of its function on the airway phosphoproteome, NEK10 was CRISPR/Cas9 targeted in human airway air-liquid interface (ALI) cultures with 2 independent guides and assayed by iron-enrichment phosphoproteomics.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Respiratory Epithelial Cell, Lung

DISEASE(S): Bronchiectasis

SUBMITTER: Raghu Chivukula

LAB HEAD: David M. Sabatini

PROVIDER: PXD016600 | Pride | 2020-01-09

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance.

Chivukula Raghu R RR Montoro Daniel T DT Leung Hui Min HM Yang Jason J Shamseldin Hanan E HE Taylor Martin S MS Dougherty Gerard W GW Zariwala Maimoona A MA Carson Johnny J Daniels M Leigh Anne MLA Sears Patrick R PR Black Katharine E KE Hariri Lida P LP Almogarri Ibrahim I Frenkel Evgeni M EM Vinarsky Vladimir V Omran Heymut H Knowles Michael R MR Tearney Guillermo J GJ Alkuraya Fowzan S FS Sabatini David M DM

Nature medicine 20200120 2

Mucociliary clearance, the physiological process by which mammalian conducting airways expel pathogens and unwanted surface materials from the respiratory tract, depends on the coordinated function of multiple specialized cell types, including basal stem cells, mucus-secreting goblet cells, motile ciliated cells, cystic fibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells<sup>1,2</sup>. Bronchiectasis, a syndrome of pathological airway dilation associated with imp ...[more]

PMID: 31959991

Similar Datasets

Changes in microRNA and mRNA expression with differentiation of human bronchial epithelial cells [mRNA]

Project description:Normal human bronchial epithelial (NHBE) cells cultured in an air-liquid interface (ALI) system form a polarized, pseudostratified epithelium composed of basal, ciliated and goblet cells that closely resemble the in vivo airway epithelium structure. ALI cultures of NHBE cells provide a unique in vitro system to investigate airway epithelial biology, including developmental, structural and physiologic aspects. In this study, we wanted to investigate mRNA expression patterns during airway epithelium differentiation. By using microarrays, we studied the changes in expression of mRNAs in normal human bronchial epithelial cells as they differentiate from an undifferentiated monolayer to a differentiated pseudostratified epithelium after 28 days of air-liquid interface (ALI) culture, when epithelial cells differentially express basal, ciliated and goblet cell markers. Normal human bronchial epithelial cells were cultured in an air-liquid interface (ALI) system and harvested at three different time-points: subconfluent, confluent and day 28 of ALI. Samples were processed for total RNA extraction and hybridization on Affymetrix microarrays. All the experiments were performed by triplicate.

2012-10-01 | E-GEOD-39059 | biostudies-arrayexpress

Changes in microRNA and mRNA expression with differentiation of human bronchial epithelial cells [miRNA]

Project description:Normal human bronchial epithelial (NHBE) cells cultured in an air-liquid interface (ALI) system form a polarized, pseudostratified epithelium composed of basal, ciliated and goblet cells that closely resemble the in vivo airway epithelium structure. ALI cultures of NHBE cells provide a unique in vitro system to investigate airway epithelial biology, including developmental, structural and physiologic aspects. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs of 20-23 nucleotides that down-regulate gene expression by either inducing degradation of target mRNAs or impairing their translation. They are phylogenetically well conserved, which probably implies an important role of miRNAs in biological processes. In this way, we wanted to shed some light on miRNA specific roles and the relationship with their mRNA targets during airway epithelium differentiation. By using microarrays, we studied the changes in expression of microRNAs in normal human bronchial epithelial cells as they differentiate from an undifferentiated monolayer to a differentiated pseudostratified epithelium after 28 days of air-liquid interface (ALI) culture, when epithelial cells differentially express basal, ciliated and goblet cell markers. Normal human bronchial epithelial cells were cultured in an air-liquid interface (ALI) system and harvested at three different time-points: subconfluent, confluent and day 28 of ALI. Samples were processed for total RNA (including small RNAs) extraction and hybridization on Affymetrix microarrays. All the experiments were performed by triplicate.

2012-10-01 | E-GEOD-39060 | biostudies-arrayexpress

miRNAs high throughput sequencing profiling of regenerating human airway epithelial cells

Project description:The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis). The airway mucociliary epithelium is consituted of three main cell types : ciliated cells, secretory cells and basal cells. We used microRNA microrrays to investigate the signature of microRNA during the four step of regeneration of the airway epithelium. Four time points (ALI-D0, ALI-D7, ALI-D14, ALI-D21) of regeneration of the airway epithelium for 3 donors.

2011-06-06 | E-GEOD-22144 | biostudies-arrayexpress

Transcriptome analysis during the time course of regeneration of the human airway mucociliary epithelium

Project description:The regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis). We used microarrays to detail the global programme of gene expression that occurs during regeneration and ciliogenesis of the human airway mucociliary epithelium. The four time points of regeneration of the airway epithelium (ALI-D0 which corresponds to the end of proliferation step; ALI-D7 which corresponds to the polarization step; ALI-D14 which corresponds to the onset of ciliogenesis and ALI-D21 corresponding to the terminal differentiation step) for RNA extraction and hybridization on Affymetrix microarrays.

2011-06-06 | E-GEOD-22142 | biostudies-arrayexpress

RNA-seq of In vitro differentiation of ciliated cells in ALI-cultured human airway epithelium

Project description:The aim of this study was to analyze gene expression of primary airway epithelial cells during their differentiation in air-liquid interface ALI culture. Cells from one healthy donor were collected at different days of ALI culture (0,6,9,14 and 21). All samples were sequenced on Illumina NovaSeq6000 platform, in 2x150 mode, with a coverage of 100M reads/sample. Obtained data was later correlated with expression of 14 genes known to be related to airway epithelium differentiation obtained using qRT-PCR technique (TaqMan low density array, TLDA cards).

2021-11-29 | E-MTAB-11209 | biostudies-arrayexpress

MicroRNA signature during the time course of regeneration of the human airway mucociliary epithelium

2011-06-06 | E-GEOD-22141 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (stem cell clones NESC,TASC,DASC)

Project description:The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel findings that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. The long-term self-renewal potential of the putative human stem cell clones (NESC,TASC,DASC) allowed us to isolate independent pedigrees for the analysis of the progeny of a single cell. Expansion of these lines yielded abundant immature cells of known pedigree for a range of differentiation assays to assess lineage potential. All stem cells were grown on feeder layer (3T3).NESC were differentiated using Air liquid interface system (ALI), 3D matrigel system (MAT) and Self assembling sphere culture(SAS). The differentiation potential of TASC and DASC were studied using ALI and MAT systems.

2011-11-01 | E-GEOD-32604 | biostudies-arrayexpress

PGC-1alpha mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

Project description:Human rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in humans and highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examined the links between viral host defense, cellular metabolism, and epithelial barrier function. We observed that early HRV-C15 infection induced a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induced ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1alpha regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

2021-04-30 | PXD024591 | Pride

Conditionally reprogrammed (CRC) and feeder free SMAD inhibited (SMADi) expanded human nasal epithelial cells label-free LC-MS/MS

Project description:Discovery of therapies that are able to correct defective CFTR requires patient derived in vitro pre-clinical cell models to be developed. Two main approaches exist to expand bronchial and nasal cultures, such as conditionally reprogrammed cells (CRC) and feeder free dual SMAD inhibition (SMADi) to overcome senescence, low cell count, and increase passages. To mimic airway epithelium the expanded cells are differentiated at air liquid Interface (ALI). This project focused to compare the global proteome of ALI differentiated CRC and SMADi expanded HNECs both treated and untreated with CFTR corrector VX-809.

2021-12-05 | PXD018386 | Pride

Transcription profiling of human airway epithelial cells sampled at multiple time points to examine mucociliary differentiation

Project description:Microarray analysis was performed to identify transcriptional changes that occur during mucociliary differentiation of human primary bronchial epithelial cells cultured at an air-liquid interface (ALI). Experiment Overall Design: Cells from three different donors were cultured and collected at 11 different time points from day 0 to day 28 of ALI culture.

2007-11-11 | E-GEOD-5264 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data