Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (ChIP-Seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Crystal Marconett
PROVIDER: E-GEOD-40394 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells). 1ug of RNA was subjected to cRNA conversion using Illumina TotalPrep RNA kit and hybridized to the HT12v4 array Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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Project description:Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells). 1ug of RNA was subjected to cRNA conversion using Illumina TotalPrep RNA kit and hybridized to the HT12v4 array Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells
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Project description:Alveoli are thin-walled sacs that serve as the gas exchange units of the lung. They are affected in devastating lung diseases including COPD, Idiopathic Pulmonary Fibrosis, and the major form (adenocarcinoma) of lung cancer, the leading cause of cancer deaths. The alveolar epithelium is composed of two morphologically distinct cell types: alveolar type (AT) 1 cells, exquisitely thin cells across which oxygen diffuses to reach the blood, and AT2 cells, specialized surfactant-secreting cells. Classical studies suggested that AT1 cells arise from AT2 cells during development and following injury, but more recent studies suggest other sources. Here we use histological and marker analysis, lineage tracing, and clonal analysis in mice to identify alveolar progenitor and stem cells and map their locations and potential in vivo. The results show that AT1 and AT2 cells arise independently during development from a bipotential progenitor. After birth, new AT1 cells derive from rare, long-lived, self-renewing AT2 cells, each producing a slowly expanding clonal focus of regenerated alveoli contiguous with the founder AT2 cell. This stem cell function of AT2 cells is broadly activated by diffuse AT1 cell injury, and AT2 self-renewal can be induced in vitro by EGF ligands and permanently activated in vivo by AT2 cell-specific targeting of the oncogenic KrasG12D allele, efficiently transforming AT2 cells into monoclonal adenomatous tumors that rapidly enlarge and prove fatal. Thus, there is a developmental switch in alveolar progenitor cells after birth, when mature AT2 cells function as facultative stem cells that contribute to local alveolar renewal, repair, and cancer. We propose that short-range signals from dying AT1 cells regulate AT2 stem cell activity: a signal transduced by EGFR-KRAS controls AT2 self-renewal and is hijacked during oncogenic transformation, and a separate signal controls reprogramming to AT1 cell fate. To compare expression between ATII and E18 BP populations, RNA was isolated from either population purified by FACS. Two populations are analyzed with 3 biological replicates per population.
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Project description:Gliomas are aggressive primary brain tumors, presenting surgery limitations due to their highly infiltrative potential. The expression of Angiotensin II (Ang II) receptors in human astrocytomas was previously associated with a poor prognosis. Accordingly, this study was undertaken to reveal the molecular mechanisms underlying Ang II actions in gliomas through the transcriptomic analysis of glioma cells exposed to Ang II. C6 glioma cells were treated with Ang II and specific antagonists of AT1 and AT2. Total RNA was isolated at three and six hours intervals and submitted to oligonucleotide microarray protocol. The differentially expressed genes were obtained by paired t-tests with p<0.05 and interpreted using Venn diagrams, functional enrichment and protein interaction network analyses. Validation of microarray results was carried out through qPCR experiments of selected genes. We found a high number of significant genes with low fold changes in gene expression at the time intervals studied. These genes were regulated in a time dependent-manner, with most gene expression changes being exclusive to one of the time intervals evaluated. Our results indicated that blocking AT1 or AT2 changed the expression of genes involved in regulation of transcription, cell cycle, cell proliferation, differentiation, apoptosis, cell adhesion, cell migration, regulation of actin cytoskeleton, protein transport and protein ubiquitination. Additionally, the signaling pathways over-represented by the significant genes were ErbB, mTOR, MAPK, neurotrophin, insulin and Wnt. Finally, interactome analyses revealed hub genes associated with cell proliferation, survival, migration, transport, structural support, neurotrophin pathway, MAPK signaling and Wnt signaling. Taken together, our findings implicate Ang II-transcriptional regulation in glioma progression by means of the modulation of genes participating in protumoral functions. This transcriptome pattern is observed upon Ang II activation of either AT1 or AT2 receptors, thereby highlighting the relevance of both receptor subtypes in glioma progression. Interactome analyses disclosed hub genes regulated by Ang II which may present higher control over their networks. These genes participate in biological functions that could enhance the degree of malignancy in gliomas and thus should be further explored. C6 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum, 100 Units/ml penicillin and 100 M-BM-5g/ml streptomycin. Cells were seeded in cell culture dishes and incubated at 37M-BM-0C/ 5% CO2 until becoming confluent. Then, these cells were pre-treated (30 minutes) with either AT1 receptor antagonist (Losartan: 10-5M) or AT2 receptor antagonist (PD123319: 10-5M) followed by Ang II treatment (10-7 M) according to the treatment scheme: Group 1 M-bM-^@M-^S control; Group 2 M-bM-^@M-^S cells only treated with Ang II; Group 3 M-bM-^@M-^S cells pre-treated (30 minutes) with Losartan and then treated with Ang II; Group 4 M-bM-^@M-^S cells pre-treated (30 minutes) with PD123319 and then treated with Ang II. To identify which genes were significantly differentially expressed, paired t-tests (p<0.05) were performed in the following comparisons: Ang II x Control (3h); Ang II x Control (6h); Ang II +Los x Ang II (3h); Ang II +Los x Ang II (6h); Ang II +PD123319 x Ang II (3h); Ang II +PD123319 x Ang II (6h).
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Project description:Alveolar epithelial cell fate decisions drive lung development and regeneration. Using transcriptomic and epigenetic profiling coupled with genetic mouse and organoid models, we identified Klf5 as a critical regulator of alveolar epithelial cell fate across the lifespan. During prenatal lung development and alveologenesis, Klf5 enforces alveolar epithelial type 1 (AT1) cell lineage fidelity. While it is dispensable for both adult AT1 and alveolar epithelial type 2 (AT2) cell homeostasis, Klf5 regulates AT2 cell plasticity after injury. Klf5 represses AT2 cell proliferation and enhances AT2-AT1 cell differentiation in a spatially restricted manner in both infectious and non-infectious models of acute respiratory distress syndrome. Moreover, ex vivo organoid assays reveal that Klf5 modulates AT2 cell fate decisions through reducing AT2 cell sensitivity to inflammatory signaling. These data highlight a major transcriptional regulator of AT1 cell lineage commitment and of the AT2 cell response to inflammatory crosstalk during lung regeneration.
2022-06-08 | GSE190676 | GEO
Project description:Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells).
2013-04-15 | GSE38569 | GEO
Project description:Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells).
2013-04-15 | GSE38570 | GEO
Project description:Alveoli are thin-walled sacs that serve as the gas exchange units of the lung. They are affected in devastating lung diseases including COPD, Idiopathic Pulmonary Fibrosis, and the major form (adenocarcinoma) of lung cancer, the leading cause of cancer deaths. The alveolar epithelium is composed of two morphologically distinct cell types: alveolar type (AT) 1 cells, exquisitely thin cells across which oxygen diffuses to reach the blood, and AT2 cells, specialized surfactant-secreting cells. Classical studies suggested that AT1 cells arise from AT2 cells during development and following injury, but more recent studies suggest other sources. Here we use histological and marker analysis, lineage tracing, and clonal analysis in mice to identify alveolar progenitor and stem cells and map their locations and potential in vivo. The results show that AT1 and AT2 cells arise independently during development from a bipotential progenitor. After birth, new AT1 cells derive from rare, long-lived, self-renewing AT2 cells, each producing a slowly expanding clonal focus of regenerated alveoli contiguous with the founder AT2 cell. This stem cell function of AT2 cells is broadly activated by diffuse AT1 cell injury, and AT2 self-renewal can be induced in vitro by EGF ligands and permanently activated in vivo by AT2 cell-specific targeting of the oncogenic KrasG12D allele, efficiently transforming AT2 cells into monoclonal adenomatous tumors that rapidly enlarge and prove fatal. Thus, there is a developmental switch in alveolar progenitor cells after birth, when mature AT2 cells function as facultative stem cells that contribute to local alveolar renewal, repair, and cancer. We propose that short-range signals from dying AT1 cells regulate AT2 stem cell activity: a signal transduced by EGFR-KRAS controls AT2 self-renewal and is hijacked during oncogenic transformation, and a separate signal controls reprogramming to AT1 cell fate.
2014-03-07 | GSE49346 | GEO