Notch Signaling in the Thyroid is Essential for Adult Homeostasis (RNAseq thyroid)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200265 | GEO | 2023/10/23
REPOSITORIES: GEO
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Project description:Notch signaling between neighboring cells vitally contributes to specifying their identity and function, during development and in the adult. Here, we demonstrate that selective blockade of the Notch ligands JAG1 and JAG2 disrupts thermoregulation in adults by decreasing circulating thyroid hormones and thyroid function. By exploiting single-cell methods to carefully evaluate the thyroid, an understudied apex endocrine organ, we discovered unexpected thyrocyte heterogeneity, marked by three distinct thyrocyte subtypes with different Notch activation patterns.
2023-10-23 | GSE200267 | GEO
Project description:Notch signaling between neighboring cells vitally contributes to specifying their identity and function, during development and in the adult. Here, we demonstrate that selective blockade of the Notch ligands JAG1 and JAG2 disrupts thermoregulation in adults by decreasing circulating thyroid hormones and thyroid function. Sequencing data in BAT demonstrates that Notch inhibition increases thermoregulation genes and this depends on thyroid hormones.
2023-10-23 | GSE200266 | GEO
Project description:VSMCs were cultured on Jag1 or IgG-coated plates as described above. RNA was extracted using RNA isolation kit (Qiagen). Reverse-transcription PCR was done with RNA-to-cDNA kit (Applied Biosystems). cDNA was run on a TaqMan Low-Density Array, human angiogenesis panel (Applied Biosystems , Cat#4378725), amplified on a 7900 HT Fast Real Time PCR system (Applied Biosystems) according to manufacturer’s instructions. Angiogenesis gene expression was screened for human aortic vascular smooth muscle cells that were plated for 18 hours on either Notch ligands (Jag1 or Jag2) as compared to appropriate IgG controls (IgG1 or IgG2).
2011-12-01 | E-GEOD-34024 | biostudies-arrayexpress
Project description:Ventricular chambers are essential for the rhythmic contraction and relaxation that occurs in every hearbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is still poorly understood. Here we show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation and later coordinates ventricular patterning and compaction with coronary vessel development to give rise to the mature chamber via a temporal sequence of ligand signalling determined by the glycosyltransferase Manic Fringe (Mfng). The early endocardial expression of Mfng favours Dll4-Notch1 signalling, Which induces trabeculation in the developing ventricle.Ventricular maturation and compaction in turn require Mfng and Dll4 downregulation in the endocardium, Which allows myocardial Jag1- And Jag2- Signalling to Notch1 in this tissue.Timely and spatial perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. Dll4 and Notch1 conditional KOs using Nfact1 and/or Tie2 driven Cre expression: RNA was isolated from pooled whole hearts of 8 (Nfact1) or 9 (Tie2) E9.5 embryos per replicate. Dll4flox;Nfatc1-Cre and WT siblings (4 KO and 4 WT replicates), Notch1flox;Nfatc1-Cre and WT siblings (3 KO and 2 WT replicates), Dll4flox;Tie2-Cre and WT siblings (3 KO and 3 WT replicates). Jag1, Jag2 and Jag1Jag2 conditional KOs using cTnT driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. Jag1flox;cTnT-Cre and WT siblings (3 KO and 3 WT replicates), Jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). Jag1flox;jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). MFng Gain Of Function using Tie2 driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. MFng;Tie2-Cre and WT siblings (4 GOF and 4 WT replicates). For Dll4, Noth1 and Jag1 KOs, libraries were prepared using the standard Illumina TrueSeq RNASeq library preparation kit and sequenced in a GAIIx Illumina sequencer using a 75bp single end elongation protocol. For Jag2 and Jag1Jag2 KOs and MFng GOF libraries were prepared prepared using the NEBNext Ultra RNA Library Prep Kit for Illumina and sequenced in a HiSeq2500 Illumina sequencer using a 61bp single end elongation protocol
2016-02-12 | E-GEOD-67889 | biostudies-arrayexpress
Project description:Comparison of cistromes from PAX8, NKX2.1, and FOXE1 ChIP-Seq analysis using mouse thyroid gland and rat thyrocyte PCCl3 cells revealed that there is a significant overlap between GLIS3 binding regions and those of PAX8, NKX2.1, and FOXE1 in genes associated with thyroid hormone biosynthesis.
2023-04-06 | GSE207777 | GEO
Project description:Salivary adenoid cystic carcinoma (ACC) is a rare but biologically unique biphasic tumor, consisting of malignant myoepithelial and luminal epithelial cells. MYB and Notch signaling have been implicated in the pathophysiology of these tumors, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilized single cell RNA-sequencing to profile human head and neck ACC, including the first comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering previously unappreciated diversity in myoepithelial and luminal cell expression. We discover differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We further validated this selective expression in three published cohorts of ACC patients. Our data provide a potential explanation for the biphasic nature of low and intermediate grade ACC and may help direct new therapeutic strategies against these tumors.
2022-10-26 | GSE210171 | GEO
Project description:Background: Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process is unknown Results: The objective of this study was to define the role of the Notch ligand JAG1 in regulating BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. Conclusions: These data demonstrate JAG1 mediated Notch signaling regulates differentiation of BC into secretory cells. This study demonstrates that expression of the Notch ligand JAG1 is highly enriched in basal stem/progenitor cells (BC) of the human airway epithelium and that modulation of its expression levels during differentiation of BC play an important role in regulating secretory cell differentiation with no effect on ciliated cell differentiation. These observations have implications for developing novel targets to specifically modulate levels of secretory cells in human airway disorders.
2017-08-23 | GSE76421 | GEO
Project description:Ventricular chambers are essential for the rhythmic contraction and relaxation that occurs in every hearbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is still poorly understood. Here we show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation and later coordinates ventricular patterning and compaction with coronary vessel development to give rise to the mature chamber via a temporal sequence of ligand signalling determined by the glycosyltransferase Manic Fringe (Mfng). The early endocardial expression of Mfng favours Dll4-Notch1 signalling, Which induces trabeculation in the developing ventricle.Ventricular maturation and compaction in turn require Mfng and Dll4 downregulation in the endocardium, Which allows myocardial Jag1- And Jag2- Signalling to Notch1 in this tissue.Timely and spatial perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies.
2016-02-12 | GSE67889 | GEO
Project description:The inhibitory effect of supra physiological iodide concentrations on thyroid hormone synthesis (Wolff-Chaikoff effect) and thyrocyte proliferation is largely know as iodine autoregulation. However, the molecular mechanisms by which iodide excess modulate thyroid functions remains unclear. In this work, we analyzed the rat follicular cell PCCl3 transcriptome profile under untreated and treated conditions with 10-3M sodium iodide (Na/I). Serial Analysis of Gene Expression revealed several transcripts differentially expressed in response to the iodide showing that excess iodide affects almost all aspects of thyroid cell function and differentiation acting on the iodine autoregulatory mechanism through a complex process. Keywords: comparative genomic analysis PCCl3 cells were cultured under untreated and treated conditions with 10-3M NaI during 24 hours
2007-11-01 | E-GEOD-7174 | biostudies-arrayexpress
Project description:Thyroid Transcription Factor-1 (TTF-1) is a key regulator of thyroid development and function. In order to identify the genes whose expression depends on TTF-1 transcriptional activity within the thyrocyte we analyzed the consequence of the functional inactivation of this factor in PCCl3 cells. The expression of a fusion protein composed of the DNA binding domain of TTF-1 and of the strong repressive domain of the Engrailed protein (Engr HD) resulted in a dramatic loss of epithelial cell morphology and in proliferation arrest. These changes were reversed when the inhibition of endogenous TTF-1 was relieved. No change was observed when a similar fusion protein containing point mutations abolishing DNA binding activity (Engr HDm) was produced in the cells.
2012-07-01 | GSE35623 | GEO