Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA92821 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Type II cell differentiation and expression of the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) are markedly induced by cAMP and inhibited by TGF-β. cAMP induction of SP-A promoter activity is mediated by increased phosphorylation and in vivo binding of TTF-1/Nkx2.1, a critical transcription factor in lung development. To further define mechanisms for developmental induction of surfactant synthesis in HFL, herein, we investigated the potential role of microRNAs (miRNAs, miRs). To identify and characterize differentially regulated miRNAs in mid-gestation HFL explants during type II pneumocyte differentiation in culture, we performed miRNA microarray analysis of RNA isolated from epithelial cells from midgestation HFL explants before and after culture ± Bt2cAMP. Interestingly, the miR-200 family was significantly upregulated during type II cell differentiation; miR-200 family induction was inversely correlated with expression of its known targets, transcription factors ZEB1 and ZEB2, and TGF-b2. miR-200 antagonists inhibited TTF-1 and SP-A expression and upregulated TGF-β2 and ZEB1 expression in type II cells. Overexpression of ZEB1 in cultured type II cells decreased DNA binding of endogenous TTF-1, blocked cAMP stimulation of SP-A and inhibited miR-200 expression,whereas, cAMP markedly inhibited ZEB1/2 and TGF-β. Importantly, overexpression of ZEB1 or miR-200 antagonists in HFL type II cells markedly suppressed accumulation of lamellar bodies, organelles that store surfactant. Our findings suggest that the miR-200 family and ZEB1, which exist in a double-negative feedback loop regulated by TGF-β, serve important regulatory roles in the developmental regulation of type II cell differentiation and SP-A expression in HFL.
2015-10-01 | GSE61183 | GEO
Project description:Metabolism is vital to cellular function and tissue homeostasis during human lung development. In utero, embryonic pluripotent stem cells undergo endodermal differentiation towards a lung progenitor cell fate that can be mimicked in vitro using induced human pluripotent stem cells (hiPSCs) to study genetic mutations. To identify differences between wild type and surfactant protein B (SFTPB)-deficient cell lines during endoderm specification towards lung, we used an untargeted metabolomics approach to evaluate the developmental changes in metabolites. We found that the metabolites most enriched during the differentiation from pluripotent stem cell to lung progenitor cell, regardless of cell line, were sphingomyelins and phosphatidylcholines, two important lipid classes in fetal lung development. The SFTPB mutation had no metabolic impact on early endodermal lung development. The identified metabolite signatures during lung progenitor cell differentiation may be utilized as biomarkers for normal embryonic lung development.
2021-06-29 | ST002055 | MetabolomicsWorkbench
Project description:In vitro differentiation of human stem cells can produce pancreatic beta cells, the insulin-secreting cell type whose loss underlies Type 1 Diabetes. As a step towards mastery of this process, we report on transcriptional profiling of >100,000 individual cells sampled during in vitro beta cell differentiation and describe the cells that emerge. We resolve populations corresponding to beta cells, alpha-like poly-hormonal cells, non-endocrine cells that resemble pancreatic exocrine cells and a previously unreported population resembling enterochromaffin cells. We show that the beta and alpha-like cells are stable for weeks in culture without exogenous growth factors and that gene expression changes associated with in vivo beta cell maturation are recapitulated in vitro. We demonstrate that stem-cell derived enterochromaffin cells can synthesize and secrete serotonin in vitro. To remove exocrine cells, we characterize a scalable re-aggregation technique that efficiently selects endocrine cells. Finally, we use a high-resolution sequencing time course to characterize gene expression dynamics during human pancreatic endocrine induction from which we develop a lineage model of in vitro beta cell differentiation. This study provides a deeper perspective on the current state of human stem cell differentiation and is a jumping-off point for future endeavors in in vitro differentiation of pancreatic islet cells and their application in regenerative medicine.
2019-05-10 | GSE114412 | GEO
Project description:To decipher the populations of cells present in the human fetal pancreas and their lineage relationships, we developed strategies to isolate pancreatic progenitors, endocrine progenitors and endocrine cells. Transcriptome analysis of the individual populationsrevealed a large degree of conservation among vertebrates in the drivers of gene expression changes occurring at different steps of differentiation, althoughnotably, sometimes, different members of the same gene family are expressed. The transcriptome analysis establishes a resource to identify novel genes and pathways involved in human pancreas development. Single cell profiling further captured intermediate stages ofdifferentiation and enabled us to decipher the sequence of transcriptional events occurring during human endocrine differentiation. Furthermore, we evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural processoccurring in human fetuses. This comparison uncovers a few differences at the progenitor steps, a convergence at the steps of endocrine induction and the current inability to fully resolve endocrine cell subtypes in vitro.
| EGAS00001003127 | EGA
Project description:Genome profiling of mouse pulmonary epithelial type II cells
| PRJNA135711 | ENA
Project description:Low serum levels or deficiency of 1α,25-dihydroxyvitamin D3 (VD3) are associated with a higher mortality in trauma patients with sepsis or acute respiratory distress syndrome, although the molecular mechanisms behind this observation are not yet understood. VD3 is known to stimulate lung maturity, alveolar type II cell differentiation and pulmonary surfactant synthesis. This study aims to expand the knowledge by quantitative characterization of NCI-H441 cells upon VD3 treatment at the proteome level.
2023-05-10 | PXD040622 | Pride
Project description:The purpose of this study was to determine the miRNA expression profile of in vitro differentiation of human skeletal muscle cells and to couple changes in individual miRNA expression to transcriptional output of target genes. miRNA expression profiling at six different time points during the in vitro differentiation process of human skeletal muscle cells from six subjects. RNA was harvested from myoblasts before induction of differentiation and at every other day for 10 following days.
2014-12-13 | GSE53383 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a type of pulmonary fibrosis, a disease that results in scarring and stiffness of lung tissue affecting over 5 million people globally, while the underlying disease mechanisms in IPF are largely unknown. As an animal model of IPF, a single intratracheal injection of bleomycin (BLM) is generally employed, in which cell death of type II alveolar epithelial cells (AEC II) is a trigger of pulmonary fibrosis. One of mitogen-activated protein kinases, p38 is well known as an important regulator of inflammatory responses and cell fate such as apoptosis, differentiation and tumorgenesis. Given that mice with different intrinsic activity of p38 in AEC II were subjected to BLM instillation and investigated, candidate genes in the development of pulmonary fibrosis would be screened. Here, we provide gene expression profiling of lung tissues using the RNA sequencing for identifying changes in gene expression.
2020-09-09 | GSE154074 | GEO
Project description:We investigated whether in vitro expansion of human alveolar epithelial type II cells is possible. We found that human endogenous human alveolar epithelial type II cells can be cultured and passaged. The culture system enabled retroviral gene transduction into human alveolar epithelial type II cells. We performed RNA sequencing of human alveolar epithelial type II cells transduced with mutant surfactant protein C or control vector.
2019-06-27 | GSE128291 | GEO
Project description:Human VECs are categorized into two groups according to their effects on the proliferation of vascular smooth muscle cells (in vitro) and the induction of stenosis in endothelia-removed arteries after transplantation (In vivo): pro-proliferative/pro-stenotic (Type-I) virsus anti-proliferative/anti-stenotic (Type-II) VECs. Since RGS5, which is a master gene responsible for aging- and oxidative stress-dependent Type-II to Type-I conversion, is the only protein-coding gene that shows differential expression profiles between Type-I and Type-II VECs, non-coding RNAs including miRNA should be working at the downstream of RGS5 for quality control of VECs.
2020-07-27 | GSE102205 | GEO