Similar Datasets
Project description:Pax1 and Pax9 play redundant, synergistic functions in the patterning and differentiation of the sclerotomal cells that give rise to the vertebral bodies and intervertebral discs (IVD) of the axial skeleton. Gene expression profiling of an enriched population of Pax1/Pax9-expressing cells of the embryonic IVD revealed that Pax1 and Pax9 regulate cell proliferation, cartilage development, collagen fibrillogenesis and other processes vital in early IVD morphogenesis. Twenty-nine of the Pax1/Pax9 targets are also associated with axial skeletal defects that phenocopy Pax1/Pax9-deficient mice. Pax1 likely auto-regulates itself and is up-regulated in the absence of Pax9, clarifying how it compensates for the loss of Pax9, while Pax9 is unaffected by the loss of Pax1. Pax1 and Pax9 positively regulate several of the cartilage development genes known to be regulated by the “Sox trio” (Sox5/Sox6/Sox9).
2017-08-25 | GSE63017 | GEO
Project description:Small cell lung cancer (SCLC) is a more aggressive and deadlier form of lung cancer with limited effective therapies currently available. By utilizing a genome-wide CRISPR-Cas9 dropout screen, we have identified the Paired box protein 9 (PAX9) as an essential factor for the cell viability of SCLC-A type, which accounts for approximately 70% of all SCLC. PAX9 is transcriptionally driven by the BAP1/ASXL3/BRD4 epigenetic axis and is overexpressed in human malignant SCLC tumor samples. Genome-wide studies have revealed that PAX9 occupies distal enhancer elements and represses gene expression by restricting enhancer activity. Genetic depletion of PAX9 leads to a dramatic induction of a primed-active enhancer transition, resulting in an increased expression of a large number of neural differentiation and tumor-suppressive genes in multiple SCLC cell lines. Mechanistically, PAX9 interacts and co-functions with the Nucleosome Remodeling and Deacetylase (NuRD) complex at enhancers and they repress the nearby gene expression, which could be rescued by pharmacological HDAC inhibition. Overall, this study provides mechanistic insight into the oncogenic function of the PAX9/NuRD complex epigenetic axis in human SCLC and suggests that re-activation of the primed enhancers may have therapeutic efficacy in treating SCLC-A type cancers expressing high levels of PAX9.
2021-08-03 | GSE164247 | GEO
Project description:The aim of this study was to identify differentially expressed genes within the pharyngeal arches of Pax9-null embryos at E9.5. Mice null for Pax9 die in the neonatal period with complex cardiovascular defects, caused by abnormal morphogenesis of the pharyngeal arch arteries.
2019-08-28 | GSE128087 | GEO
Project description:The caudal fin is an anomaly among vertebrate locomotory appendages: its internal skeleton is as asymmetric as the human hand, but it lacks the Shh-secreting Zone of Polarizing Activity (ZPA) and the Gli3/HoxD/Hand2 programs that govern anterior-posterior patterning in other appendages. As the caudal fin was also the first appendage to evolve, deciphering its alternative patterning program may provide clues to the ancestral state. Pax9 is one of few conserved appendage patterning factors reported to also be active in the caudal fin, specifically in the anterior domain. We report that loss of pax9 function in zebrafish not only disrupts anterior-specific caudal fin anatomy, but also results in a spectacular fusion of the caudal and anal fins along the ventral midline. The dorsal fin is also expanded to a lesser degree, the paired fins not at all. The mutant caudal fin initially forms as an irregularly patterned structure lacking anterior molecular identity, with supernumerary elements spilling out beyond the normal anterior boundary. Unexpectedly, this phenotype is subsequently compounded by neighboring trunk somites erroneously deploying skeletal mesenchyme in the normally finless caudal peduncle region, completing the ectopic skeleton. scRNAseq analysis at caudal fin bud stage indicates that pax9 mutants gain skeletal mesenchyme at the expense of a specialized type of fibroblast involved in the formation of fin fold actinotrichia. Median fin skeletal mesenchyme and fin fold fibroblasts both arise from the sclerotome, a somite compartment that also robustly expresses pax9. We propose that, within the sclerotome, Pax9 pushes progenitors towards fin fold fibroblast fate, limiting how many cells will later be available to make median fin skeleton. Within the fin bud, it drives anterior identity, with the strongest impact on the ZPA-free caudal fin bud. These dual sites of action make Pax9 a uniquely powerful governor of median fin development.
2026-06-18 | GSE328963 | GEO
Project description:Nonsyndromic clefts of the palate and/or lip are common birth defects arising in about 1/700 live births worldwide. They are caused by multiple genetic and environmental factors, can only be corrected surgically and require complex post-operative care that imposes significant burdens on individuals and society. Our understanding of the molecular networks that control palatogenesis has advanced through studies on mouse genetic models of cleft palate. In particular, the transcription factor Pax9 regulates palatogenesis through the Bmp, Fgf and Shh pathways in mice. But there is still much to learn about Pax9’s relationship with other signaling pathways in this process. Expression analyses and unbiased gene expression profiling studies offer a molecular explanation for the resolution of palatal defects by showing that Wnt and Eda/Edar-related genes are expressed in normal palatal tissues and that the Wnt and Eda/Edar signaling pathway is downstream of Pax9 in palatogenesis.
2017-08-15 | GSE89603 | GEO
Project description:Cell fate determination and maintenance play critical roles in establishing and preserving tissue identity and function during organ development. Aberrant cell fate transitions can lead to cancer cells acquiring lineage plasticity, resulting in tumor heterogeneity and resistance to treatment. Trp63 (p63) is a transcription factor important for the formation of stratified squamous epithelium in the esophagus. Here, we report an unexpected role of p63 in protecting esophageal basal progenitor cells from committing to a neuroendocrine fate. Combination of single cell RNA sequencing analysis, lineage tracing and in vitro differentiation, we found that deletion of p63 in developing murine esophagus and in human embryonic stem cells results in extensive differentiation towards neuroendocrine lineage.
2024-07-25 | GSE263694 | GEO
Project description:Periodontal ligament stem cells (PDLSCs) play central roles in periodontal ligament (PDL) tissue homeostasis, repair, and regeneration. Previously, we established a protocol to differentiate human induced pluripotent stem cell-derived neural crest-like cells (iNCs) into PDLSC-like cells (iPDLSCs) using human PDL cell-derived extracellular matrix (ECM). However it remained unclear what factors principally regulate the differentiation of iNCs into iPDLSCs. In this study, we aimed to identify the transcription factor regulating production of human PDL cell-derived ECM, which is responsible for the generation of iPDLSCs. We cultured iNCs on two human PDL cell lines (HPDLC-3S and HPDLC-3U) and human dermal fibroblasts (HDF). iNCs cultured on HPDLC-3U showed higher iPDLSC-associated gene expression and mesenchymal differentiation capacity than cells cultured on HDF or HPDLC-3S. The transcription factor PAX9 was highly expressed in HPDLC-3U compared with HDF and HPDLC-3S. iNCs cultured on siPAX9-transfected HPDLC-3U displayed downregulation of iPDLSC-associated marker expression and adipocytic differentiation capacity relative to controls. Our findings suggest that PAX9 is one of the transcription factors regulating ECM production in human PDL cells, which is responsible for the differentiation of iNCs into iPDLSCs.
2022-07-18 | GSE208250 | GEO
Project description: Not available
| S-EPMC7349584 | biostudies-literature
Project description: Not available
| S-EPMC5842438 | biostudies-literature
Project description:PPARg is a nuclear receptor that plays an important role in lipid metabolism, homeostasis and immunity. Microarray analysis of gene expression was performed in macrophages from WT and PPARg KO mice. Differentially expressed genes were selected for further analysis.
2010-09-24 | GSE24292 | GEO