Sp3 is essential for normal lung morphogenesis and cell cycle progression during mouse embryonic development
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ABSTRACT:
PROVIDER: PRJNA937194 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23565700.fastq.gz | Fastqsanger.gz | |||
| SRR23565701.fastq.gz | Fastqsanger.gz | |||
| SRR23565702.fastq.gz | Fastqsanger.gz | |||
| SRR23565703.fastq.gz | Fastqsanger.gz | |||
| SRR23565704.fastq.gz | Fastqsanger.gz |
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Project description:Members of the Sp family of transcription factors regulate gene expression via binding GC boxes within promoter regions. Unlike Sp1, which stimulates transcription, the closely related Sp3 can either repress or activate gene expression and is required for perinatal survival in mice. Here we use RNAseq and cellular phenotyping to show how Sp3 regulates murine fetal cell differentiation and proliferation. Homozygous Sp3-/- mice were smaller than WT and Sp+/- littermates, died soon after birth, and had abnormal lung morphogenesis. RNAseq of Sp3-/- fetal lung mesenchymal cells identified alterations in extracellular matrix production, developmental signaling pathways, and myofibroblast/lipofibroblast differentiation. The lungs of Sp3-/- mice contained multiple structural defects, with abnormal endothelial cell morphology, lack of elastic fiber formation, and accumulation of lipid droplets within mesenchymal lipofibroblasts. Sp3-/- cells and mice also displayed cell cycle arrest, with accumulation in G0/G1 and reduced expression of numerous cell cycle regulators including Ccne1. These data detail the global impact of Sp3 on in vivo mouse gene expression and development. Development • Accepted manuscript lung mesenchymal cells identified alterations in extracellular matrix production, developmental signaling pathways, and myofibroblast/lipofibroblast differentiation. The lungs of Sp3-/- mice contained multiple structural defects, with abnormal endothelial cell morphology, lack of elastic fiber formation, and accumulation of lipid droplets within mesenchymal lipofibroblasts. Sp3-/- cells and mice also displayed cell cycle arrest, with accumulation in G0/G1 and reduced expression of numerous cell cycle regulators including Ccne1. These data detail the global impact of Sp3 on in vivo mouse gene expression and development.
2023-02-28 | GSE225703 | GEO
Project description:Members of the Sp family of transcription factors regulate gene expression via binding GC boxes within promoter regions. Unlike Sp1, which stimulates transcription, the closely related Sp3 can either repress or activate gene expression and is required for perinatal survival in mice. Here, we use RNA-seq and cellular phenotyping to show how Sp3 regulates murine fetal cell differentiation and proliferation. Homozygous Sp3-/- mice were smaller than wild-type and Sp+/- littermates, died soon after birth and had abnormal lung morphogenesis. RNA-seq of Sp3-/- fetal lung mesenchymal cells identified alterations in extracellular matrix production, developmental signaling pathways and myofibroblast/lipofibroblast differentiation. The lungs of Sp3-/- mice contained multiple structural defects, with abnormal endothelial cell morphology, lack of elastic fiber formation, and accumulation of lipid droplets within mesenchymal lipofibroblasts. Sp3-/- cells and mice also displayed cell cycle arrest, with accumulation in G0/G1 and reduced expression of numerous cell cycle regulators including Ccne1. These data detail the global impact of Sp3 on in vivo mouse gene expression and development.
| S-EPMC10110423 | biostudies-literature
Project description:Mice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. ( Keywords: Transcription factors, Sp3, knockout mice, cardiac malformations, E12.5
2007-11-01 | GSE9124 | GEO
Project description:Multiple sclerosis (MS) is an inflammatory disease of the central nervous system and is generally considered to be autoimmune in nature. We previously demonstrated that the transcription factor Sp3 is significantly down-regulated in immune cells from MS patients. The potential role of Sp3 down-regulation in MS pathogenesis is not well understood. The function of endogenous Sp3 was assessed in vitro after siRNA-mediated knockdown of its transcript in Jurkat cells. Sp3 protein levels were reduced an average of 70%. ELISA studies demonstrated decreased endogenous production of IL-10 and TGFβ1 and increased endogenous production of TNFα (p<0.05 in all assays). Subsequent microarray analysis demonstrated significantly altered expression of 36 genes (p<0.001 for each gene) compared with control samples. Analysis showed differential expression (p<0.005) of 8 gene pathways. Many of the genes and pathways that were regulated by Sp3 are involved in immune function, specifically with regard to apoptosis, cell-to-cell adhesion, integrin signaling, T-cell differentiation, and cytokine production. This study identifies mechanisms by which Sp3 may regulate immune function and suggests a basis for its potential contribution to MS disease pathogenesis. Experiment Overall Design: Two Sp3 siRNA knockdown groups (siRNA Sp3 #2: n=3, and #6: n=3) were clustered together into the Treated condition, and the two control groups (siRNA for GAPDH: n=3, and Non-transfected cells: n=3)were assembled to constitute the Control condition. Thus a total of 12 arrays (6 Controls and 6 treated) were used in this experiment.
2008-04-07 | E-GEOD-7102 | biostudies-arrayexpress
Project description:Mice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. ( Experiment Overall Design: Hearts were dissected from E12.5 wildtype (n=3) and Sp3 knockout (n=3) fetuses. Total RNA was isolated from individual hearts; 5μg was used for labelling and hybridization to 430 2.0 Gene Chips (a total of 6).
2008-06-17 | E-GEOD-9124 | biostudies-arrayexpress
Project description:Sp1 and Sp3 belong to the Specificity proteins (Sp)/Krüppel-like transcription factor family. They are closely related, ubiquitously expressed and recognize G-rich DNA motifs. They are thought to regulate generic processes such as cell cycle and growth control, metabolic pathways and apoptosis. Ablation of Sp1 or Sp3 in mice is lethal, and combined haploinsufficiency results in hematopoietic defects during the fetal stages. Here, we show that in adult mice conditional ablation of either Sp1 or Sp3 has minimal impact on hematopoiesis, while the simultaneous loss of Sp1 and Sp3 results in severe macrothrombocytopenia and platelet dysfunction. We employed flow cytometry, cell culture and electron microscopy and show that although megakaryocyte numbers are normal in bone marrow and spleen, they display a less compact demarcation membrane system and a striking inability to form proplatelets. Through megakaryocyte transcriptomics and platelet proteomics we identified several cytoskeleton-related proteins and downstream effector kinases, including Mylk, that were downregulated upon Sp1/Sp3 depletion, providing an explanation for the observed defects in megakaryopoiesis. We show that Mylk is required for proplatelet formation and stabilization and for ITAM-receptor mediated platelet aggregation. Our data highlights the specific vs generic role of these ubiquitous transcription factors in the highly specialized megakaryocytic lineage.
2014-12-18 | GSE58707 | GEO
Project description:Sp1 and Sp3 belong to the Specificity proteins (Sp)/Krüppel-like transcription factor family. They are closely related, ubiquitously expressed and recognize G-rich DNA motifs. They are thought to regulate generic processes such as cell cycle and growth control, metabolic pathways and apoptosis. Ablation of Sp1 or Sp3 in mice is lethal, and combined haploinsufficiency results in hematopoietic defects during the fetal stages. Here, we show that in adult mice conditional ablation of either Sp1 or Sp3 has minimal impact on hematopoiesis, while the simultaneous loss of Sp1 and Sp3 results in severe macrothrombocytopenia and platelet dysfunction. We employed flow cytometry, cell culture and electron microscopy and show that although megakaryocyte numbers are normal in bone marrow and spleen, they display a less compact demarcation membrane system and a striking inability to form proplatelets. Through megakaryocyte transcriptomics and platelet proteomics we identified several cytoskeleton-related proteins and downstream effector kinases, including Mylk, that were downregulated upon Sp1/Sp3 depletion, providing an explanation for the observed defects in megakaryopoiesis. We show that Mylk is required for proplatelet formation and stabilization and for ITAM-receptor mediated platelet aggregation. Our data highlights the specific vs generic role of these ubiquitous transcription factors in the highly specialized megakaryocytic lineage. Megakaryocyte mRNA profiles of Sp1fl/fl::Sp3fl/fl (WTlox) and Pf4-Cre::Sp1fl/fl::Sp3fl/fl (dKO) mice were generated by deep sequencing, in triplicate.
2014-12-18 | E-GEOD-58707 | biostudies-arrayexpress
Project description:SP1 and SP3 have been reported to play an critical role in the pregression of tumors. In order to elucidate the molecular mechanism of SP1 and SP3 in colorectal cancer, RNA-seq analysis was performed on SP1 and SP3 knockdown and control HCT116 cells.
2024-07-01 | GSE179314 | GEO
Project description:The histone deacetylase HDAC2, which negatively regulates neuronal plasticity and synaptic gene expression, is upregulated both in Alzheimer’s disease (AD) patients and mouse models (Graff et al., 2012). Therapeutics targeting HDAC2 are speculated to be a promising avenue for ameliorating AD related cognitive impairment. However, attempts to generate HDAC2-specific inhibitors have not been successful. Here, we take a novel approach utilizing integrative genomics to identify proteins that mediate HDAC2 recruitment to synaptic plasticity genes. Functional screening revealed that knockdown of the transcription factor Sp3 phenocopied HDAC2 knockdown, and that Sp3 facilitated the recruitment of HDAC2 to synaptic genes. Importantly, like HDAC2, Sp3 expression was elevated in AD patients and mouse models, where Sp3 knockdown ameliorated synaptic dysfunction. Furthermore, exogenous expression of an HDAC2 fragment containing the Sp3 binding domain fully restored synaptic plasticity and memory in a mouse model with severe neurodegeneration. Our findings indicate that targeting the HDAC2-Sp3 complex could enhance synaptic and cognitive function, without affecting HDAC2 function in other processes.
2017-08-08 | GSE87441 | GEO
Project description:Fibroblast growth factor (FGF) 10 is essential for lung morphogenesis
| PRJNA962857 | ENA