Similar Datasets
Project description:Differentiation of human pluripotent stem cells (hPSCs) can be used to model human heart development and, in turn, to analyze the developmental consequences of genetic abnormalities. Here, we deleted NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs) and identified a novel genetic interaction between NKX2-5 and HEY2 that is required for heart development
2018-03-21 | GSE89443 | GEO
Project description:The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To better understand how genomic alterations of NKX2-1 drive tumorigenesis, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma, and analyzed DNA binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation from NKX2-1-amplified human lung adenocarcinoma cell lines. Combining these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1, in addition to consensus binding motifs including a nuclear hormone receptor signature and a Forkhead box motif in NKX2-1-bound sequences. RNA interference analysis of NKX2-1-amplified cells compared to non-amplified cells demonstrated that LMO3 mediates cell proliferation downstream of NKX2-1; cistromic analysis that NKX2-1 may cooperate with FOXA1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transducer of lineage specific cell survival of NKX2-1-amplified lung adenocarcinomas. NKX2-1 ChIP-seq from three lung adenocarcinoma cell lines with amplification of NKX2-1
2013-01-22 | E-GEOD-39998 | biostudies-arrayexpress
Project description:Congenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFR?. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.
| S-EPMC5893543 | biostudies-literature
Project description:CHIP-seq for NKX2-3 overexpressing tumor pericytes
| PRJNA1044133 | ENA
Project description:Stem cell therapy holds great promise for the replacement of damaged or dysfunctional myocardium. Nitric oxide (NO) has been shown to promote embryonic stem (ES) cell differentiation in other systems. We hypothesized that NO, through NO synthase gene transfer or exogenous NO exposure, would promote the differentiation of mouse ES cells into cardiomyocytes (CM). In our study, NO treatment increased both the number and the size of beating foci in embryoid body (EB) outgrowths. Within 2 weeks, 69% of the inducible NO synthase-transduced EB displayed spontaneously beating foci, as did 45% of the NO donor-treated EB, compared with only approximately 15% in controls. Cardiac-specific genes and protein expression were significantly increased in NO-treated ES. Electron microscopy and immunocytochemistry revealed that these NO-induced contracting cells exhibited characteristics consistent with CM. At day 7 in culture, troponin T was expressed in 45.6 +/- 20.6% of the NO-treated ES cells but in only 9.25 +/- 1.77% of control cells. Interestingly, 50.4 +/- 18.4% of NO-treated ES cells were troponin T-negative and annexin V-positive. This apoptotic phenotype was seen in <1% of the control ES cells. These data strongly support our hypothesis that mouse ES cells can be accelerated to differentiate into CM by NO treatment. NO may influence cardiac differentiation by both inducing a switch toward a cardiac phenotype and inducing apoptosis in cells not committed to cardiac differentiation.
| S-EPMC514469 | biostudies-literature
Project description:To determine how SAHA-PIP G can trigger the expression of the mesendoderm-related genes in mouse ES cells, chromatin immunoprecipitation (ChIP-seq) analysis was carried out with an antibody against the histone H3 lysine 4 trimethylation (H3K4me3) using EBs harvested on day 0
2020-01-03 | GSE142857 | GEO
Project description:The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To better understand how genomic alterations of NKX2-1 drive tumorigenesis, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma, and analyzed DNA binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation from NKX2-1-amplified human lung adenocarcinoma cell lines. Combining these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1, in addition to consensus binding motifs including a nuclear hormone receptor signature and a Forkhead box motif in NKX2-1-bound sequences. RNA interference analysis of NKX2-1-amplified cells compared to non-amplified cells demonstrated that LMO3 mediates cell proliferation downstream of NKX2-1; cistromic analysis that NKX2-1 may cooperate with FOXA1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transducer of lineage specific cell survival of NKX2-1-amplified lung adenocarcinomas.
2013-01-22 | GSE39998 | GEO
Project description:ChIP-seq was performed to identify the binding regions of SPDEF and NKX2-1 in A549 lung carcinoma cells expressing NKX2-1 and SPDEF.
2017-03-02 | GSE86957 | GEO
Project description:We report the identification of genome-wide binding site of the cardiac transcription factor Nkx2-5 during mouse heart development. Examination of Nkx2-5 binding in wild-type mouse in duplicate.
2015-09-02 | E-GEOD-44574 | biostudies-arrayexpress
Project description:NRG-1? (neuregulin-1?) serves multiple functions during embryonic heart development by signalling through ErbB family receptor tyrosine kinases (ErbB2, ErbB3 and ErbB4). Previous studies reported that NRG-1? induces cardiomyogenesis of mESCs (mouse embryonic stem cells) at the later stages of differen-tiation through ErbB4 receptor activation. In the present study we systematically examined NRG-1? induction of cardiac myocytes in mESCs and identified a novel time window, the first 48 h, for NRG-1?-based cardiomyogenesis. At this time point ErbB3, but not ErbB4, is expressed. In contrast with the later differentiation of mESCs in which NRG-1? induces cardiomyogenesis via the ErbB4 receptor, we found that knocking down ErbB3 or ErbB2 with siRNA during the early differentiation inhibited NRG-1?-induced cardiomyogenesis in mESCs. Microarray analysis of RNA expression at this early time point indicated that NRG-1? treatment in mESCs resulted in gene expression changes important to differentiation including up-regulation of components of PI3K (phosphoinositide 3-kinase), a known mediator of the NRG-1?/ErbB signalling pathway, as well as activation of CREB (cAMP-response-element-binding protein). Further study demonstrated that the NRG-1?-induced phosphorylation of CREB was required for cardiomyogenesis of mESCs. In summary, we report a previously unrecognized role for NRG-1?/ErbB3/CREB signalling at the pre-mesoderm stage for stem cell cardiac differentiation.
| S-EPMC4654571 | biostudies-literature