Identification of a novel subset of human airway epithelial basal stem cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Mark Flory Philip Streeter
PROVIDER: MSV000095761 | MassIVE |
REPOSITORIES: MassIVE
Similar Datasets
Project description:Background. The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem / progenitor cells for the other airway cell types. The objective of this study is to better understand basal cell biology by defining the subset of expressed genes that characterize the signature of human airway epithelial basal cells. Methodology / Principal Findings. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium of healthy nonsmokers obtained by bronchial brushings in comparison to the transcriptome of the complete differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to the differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The human airway basal cell signature displayed extensive overlap with genes expressed in basal cells from other human tissues and murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the airway basal cell signature was characterized by genes encoding extracellular matrix components, and growth factors and growth factor receptors, including genes related to EGFR and VEGFR signaling. However, while human airway basal cells share similarity with basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, integrins, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion / Significance. The human airway epithelial basal cells signature identified in the present study provides novel insights into the ontogeny, molecular phenotype and biology of the stem / progenitor cells of the human airway epithelium.
2011-06-10 | GSE24337 | GEO
Project description:Background. The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem / progenitor cells for the other airway cell types. The objective of this study is to better understand basal cell biology by defining the subset of expressed genes that characterize the signature of human airway epithelial basal cells. Methodology / Principal Findings. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium of healthy nonsmokers obtained by bronchial brushings in comparison to the transcriptome of the complete differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to the differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The human airway basal cell signature displayed extensive overlap with genes expressed in basal cells from other human tissues and murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the airway basal cell signature was characterized by genes encoding extracellular matrix components, and growth factors and growth factor receptors, including genes related to EGFR and VEGFR signaling. However, while human airway basal cells share similarity with basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, integrins, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion / Significance. The human airway epithelial basal cells signature identified in the present study provides novel insights into the ontogeny, molecular phenotype and biology of the stem / progenitor cells of the human airway epithelium. This study was designed to distinguish the transcriptome of the airway epithelium basal cell from that of differentiated airway epithelium. A basal cell signature was derived and analyzed for functional significance. The signature was also evaluated as basal cells differentiated into ciliated epithelium in vitro.
2011-06-10 | E-GEOD-24337 | biostudies-arrayexpress
Project description:Basal airway epithelial cells (AEC) constitute stem/progenitor cells within the central airways and respond to mucosal injury in an ordered sequence of spreading, migration, proliferation, and dif-ferentiation to needed cell types. However, dynamic gene transcription in the early events after mucosal injury has not been studied in AEC. We examined gene expression using microarrays following mechanical injury (MI) in primary human AEC grown in submersion culture to generate basal cells and in the air-liquid interface to generate differentiated AEC (dAEC) that include goblet and ciliated cells. A select group of ~150 genes was in differential expression (DE) within 2 - 24 hr after MI, and enrichment analysis of these genes showed over-representation of functional categories related to inflammatory cytokines and chemokines. Network-based gene prioritization and network reconstruction using the PINTA heat kernel diffusion algorithm demonstrated highly connected networks that were richer in differentiated AEC compared to basal cells. Similar ex-periments done in basal AEC collected from asthmatic donor lungs demonstrated substantial changes in DE genes and functional categories related to inflammation compared to basal AEC from normal donors. In dAEC, similar but more modest differences were observed. We demon-strate that the AEC transcription signature after MI identifies genes and pathways that are im-portant to the initiation and perpetuation of airway mucosal inflammation. Gene expression oc-curs quickly after injury and is more profound in differentiated AEC, and is altered in AEC from asthmatic airways. Our data suggest that the early response to injury is substantially different in asthmatic airways, particularly in basal airway epithelial cells.
2018-01-14 | GSE109170 | GEO
Project description:To identify the RNA targets of the RNA binding proteins NONO and SFPQ in two different cell types, PARCLIP was carried out (Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) using a monoclonal antibody that recognises a NONO/SFPQ heterodimer. In this analysis, only the target gene NEAT1 was analysed, to show the binding sites for NONO and SFPQ in this transcript in the two cell lines.
2018-06-27 | GSE113349 | GEO
Project description:Background: Basal cells within the human airway epithelium constitute the stem/progenitor cells for other epithelial cell types. Basal cells respond to mucosal injury and damage to the airway mucosa in an ordered sequence of spreading, migration, proliferation and phenotype shifting (differentiation) to other needed cell types. However, dynamic gene transcription in the early events of injury and repair has not been examined in these cells. Methodology and findings: Airway epithelial cells were obtained from donated lungs and grown in submersion culture on pliable membranes to obtain a pure population of basal cells. Microarrays were used to assess the transcriptome of basal cells 8 and 24 hr after mechanical injury (MI), or to cyclic stretch (CS) in a Flexcell system (0.5 Hz, 20% distension), or both treatments. We identified 121 signature genes with > 2-fold higher differential expression (DE) 8 hr after MI; expression of nearly all of these genes returned to baseline at 24 hr after injury. In cells subjected to CS, little change in DE was noted at 8 hr, whereas at 24 hr a CS signature of 1430 DE genes were identified. The MI signature was characterized by genes encoding growth factor receptors related to the EGF pathway, IL-6, IL-8 and IL-33, extracellular matrix components, and NF-kB and p38-MAPK signaling pathways, whereas the CS signature was characterized by a broad range of genes that did not identify specific signaling pathways. Combined MI and CS at 8 hr elicited DE of down-regulated genes not seen with either stimulus alone, and at 24 hr elicited DE that was similar to that seen with CS alone. Conclusion and significance: The human airway basal epithelial cell transcription signature in the first hours after MI, after CS, and after both stimuli identifies unique differentially expressed genes and pathways that may be important in the early molecular response and biology to airway injury. Total RNA obtained from primary (AEC) and differentiated (dAEC) human airway epithelial cells subjected to 8 or 24 hours in vitro mechanical or cyclic stretch or both injuries compared to sham control as well as to type of injury. Cells were collected from four donated lungs and cultured separated in submission or air liquid interface condition prior to injury for various durations.
2015-04-30 | E-GEOD-59128 | biostudies-arrayexpress
Project description:Background: Basal cells within the human airway epithelium constitute the stem/progenitor cells for other epithelial cell types. Basal cells respond to mucosal injury and damage to the airway mucosa in an ordered sequence of spreading, migration, proliferation and phenotype shifting (differentiation) to other needed cell types. However, dynamic gene transcription in the early events of injury and repair has not been examined in these cells. Methodology and findings: Airway epithelial cells were obtained from donated lungs and grown in submersion culture on pliable membranes to obtain a pure population of basal cells. Microarrays were used to assess the transcriptome of basal cells 8 and 24 hr after mechanical injury (MI), or to cyclic stretch (CS) in a Flexcell system (0.5 Hz, 20% distension), or both treatments. We identified 121 signature genes with > 2-fold higher differential expression (DE) 8 hr after MI; expression of nearly all of these genes returned to baseline at 24 hr after injury. In cells subjected to CS, little change in DE was noted at 8 hr, whereas at 24 hr a CS signature of 1430 DE genes were identified. The MI signature was characterized by genes encoding growth factor receptors related to the EGF pathway, IL-6, IL-8 and IL-33, extracellular matrix components, and NF-kB and p38-MAPK signaling pathways, whereas the CS signature was characterized by a broad range of genes that did not identify specific signaling pathways. Combined MI and CS at 8 hr elicited DE of down-regulated genes not seen with either stimulus alone, and at 24 hr elicited DE that was similar to that seen with CS alone. Conclusion and significance: The human airway basal epithelial cell transcription signature in the first hours after MI, after CS, and after both stimuli identifies unique differentially expressed genes and pathways that may be important in the early molecular response and biology to airway injury.
2015-04-30 | GSE59128 | GEO
Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, enriches IL18Rαhi CD8+ T cells that elicit robust anti-tumor immunity in B16F10 melanoma. To investigate gene-expression profile of IL18Rαhi subset, we conducted transcriptome analysis.
2021-07-22 | GSE180439 | GEO
Project description:Eighteen hours monoclonal antibody C7 exposure
| PRJNA135441 | ENA
Project description:Rationale: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience suggests an urgent need to restore mucociliary function in the lungs following transplantation of tissue-engineered grafts, while pre-clinical studies show that seeding scaffolds with autologous mucosa improves regeneration. Recent data suggest that high epithelial cell seeding densities are required in regenerative medicine and existing techniques are inadequate to achieve coverage of clinically suitable grafts. Objectives: To define a scalable airway epithelial cell culture system to deliver airway epithelial cells to clinical grafts. Methods: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-kinase (ROCK) inhibition. Cells were analyzed using immunofluorescence, qPCR and flow cytometry to assess airway stem cell marker expression. Differentiation capacity and ciliary beat were assessed in air-liquid interface cultures. Karyotyping and an in vivo tracheal xenograft model were used to investigate the suitability of expanded cells for tracheal reconstruction. Measurements and Main Results: 3T3 feeder cells and ROCK inhibition allowed rapid expansion of airway basal stem cells. These cells were capable of multipotent airway differentiation in vitro, forming epithelia containing both ciliated and goblet lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated a decellularized tracheal scaffold in a heterotopic tracheal transplantation xenograft model. Conclusions: Our method addresses the clinical need to generate large numbers of airway basal epithelial cells in the time window demanded by clinical transplantation.
2015-10-01 | GSE69005 | GEO
Project description:Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5(+)TP63(+) basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.
| S-EPMC5035637 | biostudies-literature