Next-generation RNA Sequencing and Transcriptome Comparison of Mouse Wild Type and Mesenchymal Bmpr1a conditional knockout lungs of E15.5
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97946 | GEO | 2024/04/01
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:Lung mesenchymal knockout of transforming growth factor, beta receptor II (Tgfbr2) will lead to lung malformation, including impaired lung branching and cystic lesion. In order to understand the underlying mechanisms, total RNA of wild type and mesenchymal Tgfbr2 knockout lungs were isolated and sequenced using the next-generation RNA sequencing technique.
2021-04-20 | GSE98138 | GEO
Project description:Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, and this process is precisely governed by hormone-related signaling pathways. The BMP signaling pathway is now known to play crucial roles in all organ systems. However, the functions of BMP signaling in the mammary gland remain unclear. Here, we found that Bmpr1a is upregulated by hormone-induced Sp1 at pregnancy. Using a doxycycline (Dox)-inducible Bmpr1a conditional knockout mouse model, we demonstrated that loss of Bmpr1a results in compromised myoepithelial integrity, reduced mammary stem cells and precocious alveolar differentiation during pregnancy. Mechanistically, Bmpr1a regulates the expression of p63 and Slug, two key regulators of myoepithelial maintenance, through pSmad1/5-Smad4 complexes, and consequently activate P-cadherin during pregnancy. Collectively, these findings identify a novel role of BMP signaling in maintaining the identity of myoepithelial cells and suppressing precocious alveolar formation.
2021-03-05 | GSE164550 | GEO
Project description:Congenital diaphragmatic hernia (CDH) is a common and severe congential malformation characterized by defects in diaphragm, lung, and pulmonary vascular developent. Despite the frequency and severity of CDH, the underlying developmental mechanisms are not understood. We identified SIN3A loss of function sequence variants in two patients with CDH. To understand the genetic and developmental mechanisms of CDH, we generated Sin3a conditional knockout mice that lack Sin3a expression in the lung mesenchyme. SIN3A plays a critcal role during development, directing cell lineage specification and cell cycling. Despite this role, SIN3A sequence variants have not been reported in patients with CDH or other congential malformations. We found that Sin3a CKO mice have abnormal lung stucture at birth into adulthood. To determine the role of Sin3a in lung mesenchymal development, we performed transcriptomic analysis of Sin3a CKO and control lungs at embryonic day 16 (E16) when cell cycling defects were first evident, postnatal day 0 (P0) when lung defects were first evident, and P3 when lung phenotyopes worsened. In this dataset are expression data from dissected embryonic and postnatal lungs of Sin3a CKO and control mice. Sin3a CKO mice have conditional deletion of Sin3a in the lung mesenchyme directed by Tbx4rtta; tetocre (Tbx4rtta; tetocre; Sin3a flox/flox CKO). Control mice are heterozygous for Sin3a in the lung mesenchyme (Tbx4rtta; tetocre; Sin3a flox/WT). These data were used to identify transcriptional changes due to loss of Sin3a in the lung mesenchyme.
2023-12-31 | GSE246305 | GEO
Project description:A fundamental question in developmental biology is whether there are mechanisms to detect stem cells with mutations that although do not adversely affect their viability, would compromise their ability to contribute to further development. Here we show that cell competition is a novel mechanism regulating the fitness of embryonic stem cells (ESCs). We find that ESCs displaying defective BMP signalling, defective autophagy or are tetraploid are eliminated at the onset of differentiation by wild-type cells. This elimination occurs in an apoptotic dependent manner and is mediated by secreted factors. Furthermore, during this process we find that establishment of differential cMyc levels is critical and that cMyc over-expression is sufficient to induce competitive behaviour in ESCs. Cell competition is therefore a process that allows recognition and elimination of defective cells during the early stages of development and is likely to play important roles in tissue homeostasis and stem cell maintenance. We used microarrays to compare the gene expression profiles of Bmpr1a-/- and control embryonic stem cells (ESCs) in the ESC state and after differentiation in N2B27 Microarray profiles of control and Bmpr1a-/- mouse embryonic stem cells in embryonic stem cell culture media and in N2B27
2013-06-20 | E-GEOD-48092 | biostudies-arrayexpress
Project description:Hormone-responsive Bmpr1a maintains myoepithelial integrity during pregnancy
| PRJNA691166 | ENA
Project description:Lung branching morphogenesis requires reciprocal interactions between the epithelium and mesenchyme. How the lung branches are generated at a defined location and projected toward a specific direction remains a major unresolved issue. In this study, we investigated the function of Wnt signaling in lung branching in mice. We discovered that Wnt5a in both the epithelium and mesenchyme plays an essential role in controlling the position and direction of lung branching. The Wnt5a signal is mediated by Vangl1/2 to trigger a cascade of non-canonical or planar cell polarity (PCP) signaling. In response to non-canonical Wnt signaling, lung cells undergo cytoskeletal reorganization and change focal adhesions. Perturbed focal adhesions in lung explants are associated with defective branching. Moreover, we observed changes in the shape and orientation of the epithelial sheet and the underlying mesenchymal layer in regions of defective branching in the mutant lungs. Thus, PCP signaling helps define the position and orientation of the lung branches. We propose that mechanical force induced by non-canonical Wnt signaling mediates a coordinated alteration in the shape and orientation of a group of epithelial and mesenchymal cells. These results provide a new framework for understanding the molecular mechanisms by which a stereotypic branching pattern is generated.
2022-07-10 | GSE188993 | GEO
Project description:Congenital lung malformations are fatal at birth in their severe forms. Prevention and early intervention of these birth defects require a comprehensive understanding of the molecular mechanisms of lung development. We find that the loss of Inturned (Intu), a cilia and planar polarity effector gene, severely disrupts growth and branching morphogenesis of the mouse embryonic lungs. Consistent with our previous results indicating an important role for Intu in ciliogenesis and hedgehog (Hh) signaling, we find greatly reduced number of primary cilia in both the epithelial and mesenchymal tissues of the lungs. We also find significantly reduced expression of Gli1 and Ptch1, direct targets of Hh signaling, suggesting disruption of cilia-dependent Hh signaling in Intu mutant lungs. An agonist of the Hh pathway activator, smoothened, increased Hh target gene expression and tubulogenesis in explanted lungs in wild type, but not Intu mutants, suggesting impaired Hh signaling response in the absence of Intu. Furthermore, removing both Gli2 and Intu completely abolishes branching morphogenesis of the lung, strongly supporting a mechanism by which Intu regulates lung growth and patterning through cilia-dependent Hh signaling. Moreover, a transcriptomics analysis identifies around 200 differentially expressed genes (DEGs) in Intu mutant lungs, including known Hh target genes Gli1, Ptch1/2 and Hhip. Genes involved in muscle differentiation and function are highly enriched among the DEGs, consistent with an important role of Hh signaling in airway smooth muscle differentiation. In addition, we find a diminishing difference in gene expression between the left and right lungs in Intu mutants, suggesting an important role of Intu in asymmetrical growth and patterning of the mouse lungs.
2024-03-31 | GSE251669 | GEO
Project description:Congenital diaphragmatic hernia (CDH) is a common and severe congential malformation characterized by defects in diaphragm, lung, and pulmonary vascular developent. Despite the frequency and severity of CDH, the underlying developmental mechanisms are not understood. We identified SIN3A loss of function sequence variants in two patients with CDH. To understand the genetic and developmental mechanisms of CDH, we generated Sin3a conditional knockout mice that lack Sin3a expression in the lung mesenchyme. SIN3A has been shown to play a critcal role during development, directing cell lineage specification and cell cycling. We found mesenchymal progenitor cells in Sin3a CKO mice have altered expression of cell cycle progression genes from bulk lung transcriptomic analysis. To investigate changes in gene expression that occur specifically in lung mesenchymal cells, we performed fluorescent activated cell sorting (FACS) to isolate cells that underwent recombination of Sin3a. We then performed transcriptomic analysis on sorted mesenchymal cells from embryonic day 16 (E16) Sin3a CKO and control lungs. In this dataset are expression data from FACS-isolated recombined lung mesenchymal cells of Sin3a CKO and control mice. Sin3a CKO mice have conditional deletion of Sin3a in the lung mesenchyme directed by Tbx4rtta; tetocre (Tbx4rtta; tetocre; Sin3a flox/flox CKO). Control mice are heterozygous for Sin3a in the lung mesenchyme (Tbx4rtta; tetocre; Sin3a flox/WT). These data were used to identify transcriptional changes due to loss of Sin3a in the lung mesenchyme.
2023-12-31 | GSE246184 | GEO
Project description:Transcriptome analysis by RNA-seq of lungs from control and Rfwd2 epithelial-specific conditional knockout mice at embryonic 13.5 day age. RFWD2, is an E3 ubiquitin ligase that modifies specific target proteins, priming their degradation via the ubiquitin proteasome system. Rfwd2 deficiency led to a striking halt in branching morphogenesis shortly after secondary branch formation. In the mutant lung, two ETS transcript factors essential for normal lung branching, ETV4 and ETV5, were upregulated at the protein, but not transcript level. Introduction of Etv loss-of-function alleles into the Rfwd2 mutant background attenuated the branching phenotype, suggesting that RFWD2 functions at least in part through degrading ETV proteins. As a number of E3 ligases are known to target factors important for lung development, our findings provides a preview of a protein-level regulatory network essential for lung branching morphogenesis.
2016-04-28 | GSE80707 | GEO
Project description:Congenital diaphragmatic hernia (CDH) is a common and severe congential malformation characterized by defects in diaphragm, lung, and pulmonary vascular developent. Despite the frequency and severity of CDH, the underlying developmental mechanisms are not understood. We identified SIN3A loss of function sequence variants in two patients with CDH. To understand the genetic and developmental mechanisms of CDH, we generated Sin3a conditional knockout mice that lack Sin3a expression in the lung mesenchyme. SIN3A has been shown to play a critcal role during development, directing cell lineage specification and cell cycling. We found that loss of SIN3A resulted in impaired mesenchymal cell differentiation from bulk lung transcriptomic analysis in Sin3a CKO mice. To investigate the impact of loss of SIN3A in mesenchymal cell differentation, we performed fluorescent activated cell sorting (FACS) to isolate cells that underwent recombination of Sin3a. We then performed single-cell transcriptomic analysis on sorted mesenchymal cells from embryonic day 16 (E16) Sin3a CKO and control lungs. In this dataset are expression data from FACS-isolated recombined lung mesenchymal cells of Sin3a CKO and control mice. Sin3a CKO mice have conditional deletion of Sin3a in the lung mesenchyme directed by Tbx4rtta; tetocre (Tbx4rtta; tetocre; Sin3a flox/flox CKO). Control mice are heterozygous for Sin3a in the lung mesenchyme (Tbx4rtta; tetocre; Sin3a flox/WT). These data were used to identify transcriptional changes due to loss of Sin3a in the lung mesenchyme.
2023-12-31 | GSE246194 | GEO