Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE60369
PROVIDER: PRJNA258120 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63– and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63– population with failed maturation of Foxj1+ ciliated cells, as well as Scbg1a1+ and Muc5ac+ secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb+ cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63– Myb+ population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease. 12 samples, 2x2 factorial design, factor 1: time (days post-ALI), factor 2:shRNA (Myb vs Scrambled Control), performed in triplicate (biological replicates)
2014-08-12 | E-GEOD-60365 | biostudies-arrayexpress
Project description:The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63– and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63– population with failed maturation of Foxj1+ ciliated cells, as well as Scbg1a1+ and Muc5ac+ secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb+ cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63– Myb+ population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease.
2014-08-12 | GSE60365 | GEO
Project description:We have developed a new model of the human airway epithelial cell by deriving the cell-specific metabolic reactions identified from (i) a draft automated model by Wang et al. 2017 (ii) gene expression datasets of the human airway epithelial cell (Deprez et al., 2020; Braga et al., 2020). (iii) We obtained additional reactions, gene-to-reaction associations and pathways (that were not in the automated model) from HumanCyc (Trupp et al., 2010) and (iv) performed stochastic and dynamic simulations on the model generated including manual curations from primary literature and Recon3D (Brunk et al., 2018). (v) We added the viral biomass maintenance function into the model, previously developed for the macrophage cell (Renz et al. 2020) to develop the new integrated model of the human airway epithelial cell and the SARS-CoV-2 virus, (iBBEC4660).
2021-07-01 | MODEL2007210001 | BioModels
Project description:The derivation of self-renewing tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would shorten the time needed to engineer mature cell types in vitro and would have broad reaching implications for the field of regenerative medicine. Here we report the directed differentiation of human iPSCs into putative airway basal cells (“iBCs”), a population resembling the epithelial stem cell of lung airways. Using a dual fluorescent reporter system (NKX2-1GFP;TP63tdTomato) we track and purify these cells over time, as they first emerge from iPSC-derived foregut endoderm as developmentally immature NKX2-1GFP+ lung progenitors which then augment a TP63 program during subsequent proximal airway epithelial patterning. These cells clonally proliferate, initially as NKX2-1GFP+/ TP63tdTomato+ immature airway progenitors that lack expression of the adult basal cell surface marker, NGFR. However, in response to primary basal cell media, NKX2-1GFP+/ TP63tdTomato+ cells upregulate NGFR and display the molecular and functional phenotype of airway basal stem cells, including the capacity to clonally self-renew or undergo multilineage ciliated and secretory epithelial differentiation in air-liquid interface cultures. iBCs and their differentiated progeny recapitulate several fundamental physiologic features of normal primary airway epithelial cells and model perturbations that characterize acquired and genetic airway diseases. In an asthma model of mucus metaplasia, the inflammatory cytokine IL-13 induced an increase in MUC5AC+ cells similar to primary cells. CFTR-dependent chloride flux in airway epithelium generated from cystic fibrosis iBCs or their syngeneic CFTR-corrected controls exhibited a pattern consistent with the flux measured in primary diseased and normal human airway epithelium, respectively. Finally, multiciliated cells generated from an individual with primary ciliary dyskinesia recapitulated the ciliary beat and ultrastructural defects observed in the donor. Thus, we demonstrate the successful de novo generation of a tissue-resident stem cell-like population in vitro from iPSCs, an approach which should facilitate disease modeling and future regenerative therapies for a variety of diseases affecting the lung airways.Single-cell RNA-Sequencing profiling of human iPSC-derived basal cells, airway epithelium compared to primary human basal cells and airway epithelium.
2020-10-14 | GSE142246 | GEO
Project description:MYB is well recognized to be a key regulator of definitive hematopoiesis that plays an important role in the maintenance and multilineage differentiation of hematopoietic stem cells (HSCs). In the vertebrate developmental context, MYB is widely regarded dispensable for primitive hematopoiesis but critically required for the development of definitive hematopoiesis. To explore the role of MYB in human hematopoietic development we have inactivated the gene by bi-allelic TALEN-supported gene targeting in several lines of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), and subjected these cells to hematopoietic differentiation in well-defined cell culture conditions. Venus gene reporter was inserted into the knock-in allele to monitor MYB expression during the course of the hESC/iPSC differentiation. The gene reporter system showed that MYB is specifically expressed during hematopoietic commitment in the earliest primitive blood cells. Moreover, the level of MYB expression was highest at the commitment stage of differentiation and significantly decreased at the maturations stage. We found that MYB was not required for initial hematopoietic commitment of nascent mesoderm and emergence of primitive, yolk sac-type human hematopoietic progenitors. However, inactivation of MYB severely abrogated proliferation of the primitive erythroid and mixed erythroid-macrophage-megakaryocyte progenitors. In addition, MYB-negative hESC/iPSC lines demonstrated major defects in myeloid cell development and completely failed to generate mature granulocytes. Transposon-mediated rescue of MYB expression in MYB-null cells efficiently restored both the primitive hematopoietic progenitors and immature myeloid cells. Our data indicate that in contrast to its previously attributed exclusive role in definitive hematopoiesis, MYB is indispensable for primitive human hematopoiesis.
2021-01-31 | GSE125761 | GEO
Project description:Nf-kB activity is associated with the key pathological features of chronic respiratory diseases including epithelial remodelling, excess mucous production, and submucosal gland hyperplasia. However, the role of Nf-kB activity in airway epithelial differentiation remains controversial. In the present study we demonstrate that Nf-kB adaptor protein Myd88 deficiency promotes increased airway submucosal gland abundance and abnormal epithelial differentiation in proximal adult airways. Abnormal airway differentiation was not developmentally determined, became exacerbated following acute lung injury, and did not involve altered epithelial proliferation or apoptosis. Instead, we demonstrate that tracheal Myd88 deficiency promotes upregulation of a unique gene expression profile that includes activation of alternate, Myd88-independent Nf-kB signalling. Finally, we show that these effects are not intrinsically maintained in vitro using an air-liquid interface epithelial culture. This finding indicates that Myd88 deficiency promotes adult airway remodelling by regulating non-epithelial, non-cell autonomous Nf-kB activity. 20 microarray samples of whole trachea RNA in total: 5 samples wildtype control tissue 5 samples Myd88 KO control tissue 5 samples wildtype 3 day polidocanol injury tissue 5 samples Myd88 KO 3 day polidocanol injury tissue
2011-03-17 | E-GEOD-17268 | biostudies-arrayexpress
Project description:In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU2AF1, a known transcription co-factor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of up-regulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation and analysis of differentiating single basal cell clones. Lentivirus-mediated up-regulation of POU2AF1 in airway basal cells induced up-regulation of host defense genes, including MX1, IFIT3, IFITM and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a "host defense tone" even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of lentivirus mediated POU2AF1 or RFP (control) gene expression in human primary airway epithelial cells (3 samples per group). Uninfected basal cell was used as a further control. Conclusions: The genes up-regulated by POU2AF1 in human airway epithelial cells are mainly related to the intracellular or extracellular anti-pathogen response, suggesting POU2AF1 plays a role in airway epithelial host defense. This Series represents samples complementary to those in GSE60989.
2016-03-02 | E-GEOD-77658 | biostudies-arrayexpress
Project description:Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanismsof ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a novel human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, thegel gradually degraded, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increased during organoid differentiation,where inhibition of MMPs significantly suppressed the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs was found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.
2023-12-11 | GSE249160 | GEO
Project description:In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU2AF1, a known transcription co-factor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of up-regulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation and analysis of differentiating single basal cell clones. Lentivirus-mediated up-regulation of POU2AF1 in airway basal cells induced up-regulation of host defense genes, including MX1, IFIT3, IFITM and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a "host defense tone" even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of lentivirus mediated POU2AF1 or RFP (control) gene expression in human primary airway epithelial cells (3 samples per group). Uninfected basal cell was used as a further control. Conclusions: The genes up-regulated by POU2AF1 in human airway epithelial cells are mainly related to the intracellular or extracellular anti-pathogen response, suggesting POU2AF1 plays a role in airway epithelial host defense. By genome-wide-based screening, POU2AF1, a known lymphocyte transcription co-factor, was found to be expressed in human airway epithelium and regulate host defense genes. It might be a drug target as smoking-compromised host defense is associated with down-regulation of POU2AF1. In this Series, human airway epithelial cell transcriptomes (3 uninfected without treatment, 3 infected with lenti-RFP virus and 3 infected with lenti-POU2AF1 virus) were compared using massive parallel RNA sequencing (Illumina HiSeq 2000).
2016-03-02 | E-GEOD-60989 | biostudies-arrayexpress