Gene expression of mice over-expressing secretoglobin 3A2 in lung
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47931 | GEO | 2015/12/23
SECONDARY ACCESSION(S): PRJNA208377
REPOSITORIES: GEO
Similar Datasets
Project description:Secretoglobin (SCGB) 3A2 was originally identified as a downstream target in lung for the homeodomain transcription factor NKX2-1, whose null mutation resulted in severely hypoplastic lungs. A very low level of SCGB3A2 is expressed in lungs at embryonic day (E) 11.5 during mouse development, which markedly increases by E16.5, the time when lung undergoes dramatic morphological changes. These results suggest that SCGB3A2 may be involved in lung development. We used microarray to determine whether SCGB3A2 plays a role in lung development. Keywords: Response to SCGB3A2
2009-12-26 | GSE11226 | GEO
Project description:Secretoglobin (SCGB) 3A2 was originally identified as a downstream target in lung for the homeodomain transcription factor NKX2-1, whose null mutation resulted in severely hypoplastic lungs. A very low level of SCGB3A2 is expressed in lungs at embryonic day (E) 11.5 during mouse development, which markedly increases by E16.5, the time when lung undergoes dramatic morphological changes. These results suggest that SCGB3A2 may be involved in lung development. We used microarray to determine whether SCGB3A2 plays a role in lung development. Keywords: Response to SCGB3A2 DNA microarray was performed using RNAs isolated from 4 day-organ cultured Nkx2-1-null lungs with and without SCGB3A2 treatment.
2009-12-25 | E-GEOD-11226 | biostudies-arrayexpress
Project description:We report for the first time that secretoglobin (SCGB) 3A2, a novel cytokine-like molecule, predominantly expressed in pulmonary airways epithelium, drastically reduced the severity of lung fibrosis using bleomycin-induced mouse model. DNA microarrays were performed using RNAs isolated from mouse lungs in two experiments. In the first experiments, mice were adminitered intravenously SCGB3A2 or PBS once daily for a week, starting on day 14 after BLM administration, and in the second experiments, SCGB3A2 or PBS was administered intravenously for 12 hrs.
2011-04-30 | E-GEOD-21560 | biostudies-arrayexpress
Project description:Transcriptional profiling of Control and RbpjkCNULL lungs from E18.5. For microarray profiling, total RNA from E18.5 lungs was submitted for labeling and hybridization (Mouse Gene 1.0 ST Whole Genome Array, Affymetrix) to the Boston University Microarray Core facility. Clara cells (CCs) are a morphologically and operationally heterogeneous population of secretoglobin Scgb1a1-expressing secretory cells crucial for airway homeostasis and post-injury repair. Insights into the extent and origin of CC diversity have been hindered by the limited knowledge of markers of these cells and their precursors. To identify novel putative markers of CCs we characterized global changes in gene expression in embryonic lungs in which CCs were suppressed by conditional disruption of Notch signaling (Rbpjkcnull). Microarray profiling and Real Time PCR (qRT-PCR) identified eleven genes differentially downregulated in the E18.5 airways of Rbpjkcnull compared to controls, nearly half not previously known to mark CCs. Remarkably, in situ hybridization (ISH) revealed overlapping but also distinct domains of expression of these genes in E18.5 controls. Notably, Reg3g, Chad, Gabrp and Lrrc26 were selectively expressed in CCs of proximal airways and Upk3a expression was highly enriched in a CC subpopulation surrounding Neuroepithelial Bodies (NEBs). All genes expressed in the adult airways were found to be expressed in adult CCs and downregulated by selective CC ablation in a Naphthalene model of injury. Flow cytometry-based isolation of CCs from different airway regions of adult B1-EGFP reporter mice and qRT-PCR corroborated the spatial enrichment in gene expression observed by ISH. Remarkably, although, Scgb3a2, Upk3a, Cyp2f2, Cbr2, Krt15 could be detected unambiguously in airway progenitors as early as E14.5, only Scgb3a2 and Upk3a had their expression suppressed by disruption of Notch signaling, implicating both genes as the earliest markers for CC differentiation. Our study supports the idea that the diversification of the CC phenotype already arises during embryonic development and identifies candidate markers that can be used to investigate this process. Control (n=3) versus RbpjkCNULL(n=3)
2014-03-13 | E-GEOD-52926 | biostudies-arrayexpress
Project description:Many lung diseases involve alterations in the cellular identity of the lung epithelium. Improved insight into airway development and the changes to cellular identity that result from abnormal signaling may therefore improve understanding of the etiology of these complex diseases. We have previously described a protocol to generate epithelial airway spheres from human pluripotent stem cells (hPSCs), but still poorly understand the identity, development, and heterogeneity of these early airway cells. Here we use novel murine and human PSC lines to study developing secretory cells derived in vitro from hPSCs. Using an SCGB3A2CherryPicker (SC) reporter system together with population-based or single-cell global transcriptomic profiling we track, purify, and analyze hPSC-derived putative secretory airway progenitors and find that SC+ cells are enriched for expression of airway epithelial markers, including secretory cell markers, SCGB3A2 and SCGB1A1. Unexpectedly, some SC+ human cells also co-express distal type 2 cell genes, including SFTPC, ABCA3, NAPSA, CTSH and functional lamellar bodies, suggesting a significant level of plasticity within the hPSC-derived secretory population relative to concurrently generated proximal airway TP63+ cells or distal alveolar SFTPC+ cells. We establish that this plasticity is minimized by inhibiting low levels of endogenous canonical Wnt signaling post-lung specification, thus depleting the co-expressed type 2 cell program. Taken together, these findings suggest that, similar to in vivo mouse genetic models and diseased human lungs, hPSC-derived airway cells exhibit cellular plasticity in response to signaling cues, providing a human model system in which to study cellular identity in a disease-relevant context.
2018-02-28 | GSE103919 | GEO
Project description:Many lung diseases involve alterations in the cellular identity of the lung epithelium. Improved insight into airway development and the changes to cellular identity that result from abnormal signaling may therefore improve understanding of the etiology of these complex diseases. We have previously described a protocol to generate epithelial airway spheres from human pluripotent stem cells (hPSCs), but still poorly understand the identity, development, and heterogeneity of these early airway cells. Here we use novel murine and human PSC lines to study developing secretory cells derived in vitro from hPSCs. Using an SCGB3A2CherryPicker (SC) reporter system together with population-based or single-cell global transcriptomic profiling we track, purify, and analyze hPSC-derived putative secretory airway progenitors and find that SC+ cells are enriched for expression of airway epithelial markers, including secretory cell markers, SCGB3A2 and SCGB1A1. Unexpectedly, some SC+ human cells also co-express distal type 2 cell genes, including SFTPC, ABCA3, NAPSA, CTSH and functional lamellar bodies, suggesting a significant level of plasticity within the hPSC-derived secretory population relative to concurrently generated proximal airway TP63+ cells or distal alveolar SFTPC+ cells. We establish that this plasticity is minimized by inhibiting low levels of endogenous canonical Wnt signaling post-lung specification, thus depleting the co-expressed type 2 cell program. Taken together, these findings suggest that, similar to in vivo mouse genetic models and diseased human lungs, hPSC-derived airway cells exhibit cellular plasticity in response to signaling cues, providing a human model system in which to study cellular identity in a disease-relevant context.
2018-02-28 | GSE103918 | GEO
Project description:Transcriptional profiling of Control and RbpjkCNULL lungs from E18.5. For microarray profiling, total RNA from E18.5 lungs was submitted for labeling and hybridization (Mouse Gene 1.0 ST Whole Genome Array, Affymetrix) to the Boston University Microarray Core facility. Clara cells (CCs) are a morphologically and operationally heterogeneous population of secretoglobin Scgb1a1-expressing secretory cells crucial for airway homeostasis and post-injury repair. Insights into the extent and origin of CC diversity have been hindered by the limited knowledge of markers of these cells and their precursors. To identify novel putative markers of CCs we characterized global changes in gene expression in embryonic lungs in which CCs were suppressed by conditional disruption of Notch signaling (Rbpjkcnull). Microarray profiling and Real Time PCR (qRT-PCR) identified eleven genes differentially downregulated in the E18.5 airways of Rbpjkcnull compared to controls, nearly half not previously known to mark CCs. Remarkably, in situ hybridization (ISH) revealed overlapping but also distinct domains of expression of these genes in E18.5 controls. Notably, Reg3g, Chad, Gabrp and Lrrc26 were selectively expressed in CCs of proximal airways and Upk3a expression was highly enriched in a CC subpopulation surrounding Neuroepithelial Bodies (NEBs). All genes expressed in the adult airways were found to be expressed in adult CCs and downregulated by selective CC ablation in a Naphthalene model of injury. Flow cytometry-based isolation of CCs from different airway regions of adult B1-EGFP reporter mice and qRT-PCR corroborated the spatial enrichment in gene expression observed by ISH. Remarkably, although, Scgb3a2, Upk3a, Cyp2f2, Cbr2, Krt15 could be detected unambiguously in airway progenitors as early as E14.5, only Scgb3a2 and Upk3a had their expression suppressed by disruption of Notch signaling, implicating both genes as the earliest markers for CC differentiation. Our study supports the idea that the diversification of the CC phenotype already arises during embryonic development and identifies candidate markers that can be used to investigate this process.
2014-03-13 | GSE52926 | GEO
Project description:To comprehensively study the heterogeneity within distal airway epithelium, we performed single cell transcriptomic analysis of the normal human donor lung samples. Our analysis reveals that secretory (club) and basal cells in the distal lung airway epithelial cells are highly heterogenous. Further interrogation of secretory cells identified a subpopulation with potential for alveolar differentiation in vitro, implicating distal lung airway secretory cells as new candidates in alveolar repair and regeneration.
2021-12-10 | GSE130076 | GEO
Project description:The earliest morphologic evidence of changes in the airways associated with chronic cigarette smoking is in the small airways. To help understand how smoking modifies small airway structure and function, we developed a strategy using fiberoptic bronchoscopy and brushing to sample the human small airway (10th-12th order) bronchial epithelium to assess gene expression (Affymetrix HG-U133A array) in phenotypically normal smokers (n=6, 24 ± 4 pack-yr) compared to matched non-smokers (n=5). Compared to samples from the large (2nd to 3rd order) bronchi, the small airway samples had a higher proportion of ciliated cells, but less basal, undifferentiated, and secretory cells. The small, but not large, airway samples included Clara cells, a cell found only in the small airway epithelium, and the small, but not the large, airway epithelium expressed genes for the surfactant apoproteins. Despite the fact that the smokers were phenotypically normal, analysis of the small airway epithelium of the smokers compared to the non-smokers demonstrated up- and -down-regulation of genes in multiple categories relevant to the pathogenesis of chronic obstructive lung disease (COPD), including genes coding for cytokines/innate immunity, apoptosis, pro-fibrosis, mucin, responses to oxidants and xenobiotics, antiproteases and general cellular processes. In the context that COPD starts in the small airways, these changes in gene expression in the small airway epithelium in phenotypically normal smokers are candidates for the development of therapeutic strategies to prevent the onset of COPD. Experiment Overall Design: 6 smokers Experiment Overall Design: 5 non-smokers Experiment Overall Design: no replicates
2007-09-06 | E-GEOD-3320 | biostudies-arrayexpress
Project description:Gene expression in lung tissues were evallulated in SCGB3A2 knock-out mice.
2022-06-21 | GSE186515 | GEO