scholarly journals Cell shape changes during larval body plan development in Clytia hemisphaerica

2019 ◽  
Author(s):  
Yulia Kraus ◽  
Sandra Chevalier ◽  
Evelyn Houliston
Keyword(s):  
Cell Morphology ◽  
Cell Sheet ◽  
Body Plan ◽  
Confocal Imaging ◽  
Laboratory Model ◽  
Marker Genes ◽  
Mesenchymal Transition ◽  
Cellular Basis ◽  
Morphology Changes ◽  
Planula Larva

AbstractThe cnidarian “planula” larva shows radial symmetry around a polarized, oral-aboral, body axis and comprises two epithelia cell layers, ectodermal and endodermal. This simple body plan is set up during gastrulation, a process which proceeds by a variety of modes amongst the diverse cnidarian species. In the hydrozoan laboratory model Clytia hemisphaerica, gastrulation involves a process termed unipolar cell ingression, in which the endoderm derives from mass ingression of individual cells via a process of epithelial-mesenchymal transition (EMT) around the future oral pole of an epithelial embryo. This contrasts markedly from the gastrulation mode in the anthozoan cnidarian Nematostella vectensis, in which endoderm formation primarily relies on cell sheet invagination. To understand the cellular basis of gastrulation in Clytia we have characterized in detail successive cell morphology changes during planula formation by Scanning and Transmission Electron Microscopy combined with confocal imaging. These changes successively accompany epithialization of the blastoderm, EMT occurring in the oral domain through the bottle cell formation and ingression, cohesive migration and intercalation of ingressed cells with mesenchymal morphology, and their epithelialization to form the endoderm. From our data, we have reconstructed the cascade of morphogenetic events leading to the formation of planula larva. We also matched the domains of cell morphology changes to the expression of selected regulatory and marker genes expressed during gastrulation. We propose that cell ingression in Clytia not only provides the endoderm, but generates internal forces that shape the embryo in the course of gastrulation. These observations help build a more complete understanding of the cellular basis of morphogenesis and of the evolutionary plasticity of cnidarian gastrulation modes.

scholarly journals Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling

2011 ◽  
Vol 193 (2) ◽  
pp. 319-332 ◽  
Author(s):  
Tomoki Yano ◽  
Yuji Yamazaki ◽  
Makoto Adachi ◽  
Katsuya Okawa ◽  
Philippe Fort ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mdck Cells ◽  
Adherens Junctions ◽  
Cell Sheet ◽  
Body Plan ◽  
Mesenchymal Transition ◽  
Spatiotemporal Regulation ◽  
Specific Inhibitors ◽  
E Cadherin

The spatiotemporal regulation of E-cadherin expression is important during body plan development and carcinogenesis. We found that Tara (Trio-associated repeat on actin) is enriched in cadherin-based adherens junctions (AJs), and its knockdown in MDCK cells (Tara-KD cells) significantly decreases the expression of E-cadherin. Tara-KD activates Rac1 through the Trio RhoGEF, which binds to E-cadherin and subsequently increases the phosphorylation of p38 and Tbx3, a transcriptional E-cadherin repressor. Accordingly, the decrease in E-cadherin expression is abrogated by ITX3 and SB203580 (specific inhibitors of Trio RhoGEF and p38MAPK, respectively), and by dephosphomimetic Tbx3. Despite the decreased E-cadherin expression, the Tara-KD cells do not undergo an epithelial–mesenchymal transition and remain as an epithelial cell sheet, presumably due to the concomitant up-regulation of cadherin-6. Tara-KD reduces the actin-belt density in the circumferential ring, and the cells form flattened cysts, suggesting that Tara functions to modulate epithelial cell sheet formation and integrity by up-regulating E-cadherin transcription.

scholarly journals NRF1-Mediated Oncogenic Reprogramming Drives Estrogen-Induced Breast Carcinogenesis

2018 ◽  
Author(s):  
Jayanta Kumar Das ◽  
Quentin Felty ◽  
Robert Poppiti ◽  
Robert M. Jackson ◽  
Deodutta Roy
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Epithelial Mesenchymal Transition ◽  
Confocal Imaging ◽  
Cancer Tissue ◽  
Causative Role ◽  
Dependent Manner ◽  
Breast Carcinogenesis ◽  
Human Breast Cancer Tissue ◽  
Mesenchymal Transition

Transcription factor activity of the nuclear respiratory factor 1 protein (NRF1) is increased in breast cancer. Whether this gain of NRF1 activity is directly involved in breast cancer remains unknown. Herein, we report a novel oncogenic function of NRF1 supporting its causative role in breast cancer development and progression. The gain of NRF1 and/or treatment with 17β-estradiol (E2) produced heterogeneous breast cancer stem cells (BCSCs) composed of more than ten distinct cell sub-populations. Flow sorting combined with confocal imaging of markers for pluripotency, epithelial mesenchymal transition (EMT), and BCSCs phenotypically confirmed that the sub-populations of BCSCs arise from cell re-programming. Thus, we determined the molecular actions of NRF1 on its target gene CXCR4 because of its known role in the acquisition of BCSCs through EMT. CXCR4 was activated by NRF1 in a redox dependent manner during malignant transformation. NRF1-induced BCSCs were able to form xenograft tumors in vivo, while inhibiting transcription of CXCR4 prevented xenograft tumor growth. Consistent with our observation of NRF1 driven breast tumorigenesis in the experimental model, higher levels of NRF1 protein expression were also found in human breast cancer tissue specimens. This highly novel role of NRF1 in the stochastic acquisition of BCSCs and their progression to a malignant phenotype may open an entirely new research direction targeting NRF1 signaling in invasive breast cancer. Additionally, the discovery of targeting transcriptional activation of CXCR4 to inhibit NRF1-induced oncogenic transformation provides a mechanistic explanation for estrogen-dependent breast carcinogenesis and opens the new avenues for mechanistic therapeutic strategy against breast cancer.

scholarly journals Mining Prognostic Significance Genes in Human Thyroid Cancer Using Bioinformatics Analysis

2021 ◽  
Author(s):  
Hui Zhao ◽  
Pengjie Li ◽  
Junjian Li ◽  
Lian Duan ◽  
Yanzhu Jiao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Thyroid Cancer ◽  
Function Analysis ◽  
Akt Signaling ◽  
Differentially Expressed ◽  
Human Thyroid ◽  
Marker Genes ◽  
Clinical Prognosis ◽  
Mesenchymal Transition

Abstract Background Thyroid carcinoma (THC) is very common, yet its pathogenesis and the key tumor marker genes remain unclear.Methods Gene expression datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Project (TCGA) were used for gene differential expression analysis. Functional annotation analysis, Clinical prognosis analysis and Differential DNA methylation analysis were conducted on the differentially expressed genes (DEGs). Results Compared with induced pluripotent stem cells (iPSCs), 237 differentially expressed THC intersection genes derived from GEO and TCGA were obtained, of which 153 genes were closely related to clinicopathological features and prognostic effects. Biological function analysis indicated that most of these DEGs were involved in the proteinaceous extracellular matrix, epithelial-to-mesenchymal transition (EMT), and PI3K-Akt signaling pathway, resulting in effects on tumor invasion and metastasis. Finally, the results of differential methylation levels demonstrated that the high expression of 4 genes (CHI3L1, NFE2L3, S100A2, and LAMB3) was strongly correlated with the development of thyroid cancer.Conclusions Proteinaceous extracellular matrix, EMT, and PI3K-Akt signaling pathways were of great significance in the metastasis and invasion of THC. Genes such as CHI3L1, NFE2L3, S100A2, and LAMB3 were susceptible to THC.

PGE2 and thrombin induce myofibroblast transdifferentiation via activinA and CTGF in endometrial stromal cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Kazuya Kusama ◽  
Yuta Fukushima ◽  
Kanoko Yoshida ◽  
Mana Azumi ◽  
Mikihiro Yoshie ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Activin A ◽  
Tissue Growth ◽  
Marker Genes ◽  
Type I ◽  
Endometrial Stromal Cells ◽  
Mesenchymal Transition ◽  
Endometrial Cells

Abstract Endometriosis is characterized by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal hemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, menstruation-related factors, PGE2 and thrombin, a PAR1 agonist (P/T) induced epithelial-mesenchymal transition (EMT) of endometrial cells under hypoxia. However, the molecular mechanisms by which P/T induce development of endometriosis have not been fully characterized. To investigate the effects of P/T, RNA extracted from endometrial stromal cells (ESCs) treated with P/T were subjected to RNA sequence analysis, and identified activin A, FOS, GATA2 as upregulated genes. Activin A increased the expression of connective tissue growth factor (CTGF) and mesenchymal marker genes in ESCs. CTGF induced the expression of fibrosis marker type I collagen, fibronectin, and α-smooth muscle actin (αSMA), indicating fibroblast to myofibroblast transdifferentiation (FMT) of ESCs. In addition, activin A, FOS, GATA2, CTGF, and αSMA were localized in endometriosis lesions. Taken together, our data show that P/T induce changes resembling EMT and FMT in ectopic ESCs derived from retrograde menstruation, and that these are associated with fibrotic changes in the lesions. Pharmacological means that block P/T-induced activin A and CTGF signaling may be strategies to inhibit fibrosis in endometriotic lesions.

scholarly journals The Effects of Platelet-Rich and Platelet-Poor Plasma on Biological Characteristics of BM-MSCs In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jiahui Zhang ◽  
Jun Zhang ◽  
Nannan Zhang ◽  
Tao Li ◽  
Xiaohe Zhou ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Platelet Rich Plasma ◽  
Biological Marker ◽  
Marker Genes ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Platelet Poor Plasma ◽  
Pluripotency Marker ◽  
Damage Repair

Platelet-rich plasma (PRP) and its byproduct platelet-poor plasma (PPP) are rich sources of cytokines in tissue damage repair. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have received more and more attention for their ability to treat multiple diseases. The purpose of our study was to investigate the biologic action of PPP and PRP on BM-MSCs. The adipogenic potential of BM-MSCs revealed no obvious change, but the osteogenic ability of BM-MSCs was enhanced after treated with PRP. CCK8 assays and cell colony formation assays showed that PRP promoted cell proliferation, while this effect of PPP was not obvious. No obvious difference was found in cell cycle and apoptosis of BM-MSCs between PRP and PPP treatment. Expression of β-galactosidase, a biological marker of senescence, was decreased upon PRP treatment which indicated that PRP provided significant protection against cellular senescence. The migratory capacity of BM-MSCs was detected by scratch and transwell assays. The results indicated that PRP could affect the migration ability of BM-MSCs. From immunofluorescence detection and western blot, we demonstrated that the level of epithelial-mesenchymal transition-related proteins was changed and several pluripotency marker genes, including Sox2, Sall4, Oct4, and Nanog, were increased. Finally, the expression of the key signal pathway such as PI3K/AKT was examined. Our findings suggested that PRP promoted cell migration of BM-MSCs via stimulating the signaling pathway of PI3K/AKT.

scholarly journals Single-Cell Transcriptomes Reveal Characteristic Features of Mouse Hepatocytes with Liver Cholestatic Injury

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1069 ◽  
Author(s):  
Chang ◽  
Tian ◽  
Ji ◽  
Zhou ◽  
Hou ◽  
...  
Keyword(s):  
Single Cell ◽  
Disease Process ◽  
Marker Genes ◽  
Mesenchymal Transition ◽  
Injury Model ◽  
Duct Ligation ◽  
Study Gene Expression ◽  
Mouse Hepatocytes ◽  
Characteristic Features ◽  
Parenchymal Cells

Hepatocytes are the main parenchymal cells of the liver and play important roles in liver homeostasis and disease process. The heterogeneity of normal hepatocytes has been reported, but there is little knowledge about hepatocyte subtype and distinctive functions during liver cholestatic injury. Bile duct ligation (BDL)-induced mouse liver injury model was employed, and single-cell RNA sequencing was performed. Western blot and qPCR were used to study gene expression. Immunofluoresence was employed to detect the expressions of marker genes in hepatocytes. We detected a specific hepatocyte cluster (BDL-6) expressing extracellular matrix genes, indicating these hepatocytes might undergo epithelia-mesenchymal transition. Hepatocytes of BDL-6 also performed tissue repair functions (such as angiogenesis) during cholestatic injury. We also found that four clusters of cholestatic hepatocytes (BDL-2, BDL-3, BDL-4, and BDL-5) were involved in inflammatory process in different ways. To be specific, BDL-2/3/5 were inflammation-regulated hepatocytes, while BDL-4 played a role in cell chemotaxis. Among these four clusters, BDL-5 was special. because the hepatocytes of BDL-5 were proliferating hepatocytes. Our analysis provided more knowledge of hepatocyte distinctive functions in injured liver and gave rise to future treatment aiming at hepatocytes.

ErbB Receptor Activation, Cell Morphology Changes, and Apoptosis Induced by Anti-Her2 Monoclonal Antibodies

1996 ◽  
Vol 226 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Yoshiko Kita ◽  
Julia Tseng ◽  
Thomas Horan ◽  
Jie Wen ◽  
John Philo ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Morphology ◽  
Receptor Activation ◽  
Erbb Receptor ◽  
Morphology Changes

scholarly journals SMAD4 mutations do not preclude epithelial–mesenchymal transition in colorectal cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Patrick Frey ◽  
Antoine Devisme ◽  
Katja Rose ◽  
Monika Schrempp ◽  
Vivien Freihen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Expression Patterns ◽  
Human Tumor ◽  
Marker Genes ◽  
Mesenchymal Transition ◽  
Gene Regulatory

AbstractTransforming growth factor beta (TGFβ) superfamily signaling is a prime inducer of epithelial-mesenchymal transitions (EMT) that foster cancer cell invasion and metastasis, a major cause of cancer-related deaths. Yet, TGFβ signaling is frequently inactivated in human tumor entities including colorectal cancer (CRC) and pancreatic adenocarcinoma (PAAD) with a high proportion of mutations incapacitating SMAD4, which codes for a transcription factor (TF) central to canonical TGFβ and bone morphogenetic protein (BMP) signaling. Beyond its role in initiating EMT, SMAD4 was reported to crucially contribute to subsequent gene regulatory events during EMT execution. It is therefore widely assumed that SMAD4-mutant (SMAD4mut) cancer cells are unable to undergo EMT. Here, we scrutinized this notion and probed for potential SMAD4-independent EMT execution using SMAD4mut CRC cell lines. We show that SMAD4mut cells exhibit morphological changes, become invasive, and regulate EMT marker genes upon induction of the EMT-TF SNAIL1. Furthermore, SNAIL1-induced EMT in SMAD4mut cells was found to be entirely independent of TGFβ/BMP receptor activity. Global assessment of the SNAIL1-dependent transcriptome confirmed the manifestation of an EMT gene regulatory program in SMAD4mut cells highly related to established EMT signatures. Finally, analyses of human tumor transcriptomes showed that SMAD4 mutations are not underrepresented in mesenchymal tumor samples and that expression patterns of EMT-associated genes are similar in SMAD4mut and SMAD4 wild-type (SMAD4wt) cases. Altogether, our findings suggest that alternative TFs take over the gene regulatory functions of SMAD4 downstream of EMT-TFs, arguing for considerable plasticity of gene regulatory networks operating in EMT execution. Further, they establish that EMT is not categorically precluded in SMAD4mut tumors, which is relevant for their diagnostic and therapeutic evaluation.

scholarly journals Celecoxib Impairs Heart Development via  Inhibiting Cyclooxygenase-2 Activity in Zebrafish Embryos

2011 ◽  
Vol 114 (2) ◽  
pp. 391-400 ◽  
Author(s):  
Dao-jie Xu ◽  
Ji-wen Bu ◽  
Shan-ye Gu ◽  
Yi-meng Xia ◽  
Jiu-lin Du ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heart Valve ◽  
Heavy Chain ◽  
Heart Development ◽  
Heart Defects ◽  
Cyclooxygenase 2 ◽  
Confocal Imaging ◽  
Marker Genes ◽  
Zebrafish Embryos

Background Celecoxib, a cyclooxygenase-2 inhibitor, is a commonly ingested drug that is used by some women during pregnancy. Although use of celecoxib is associated with increased cardiovascular risk in adults, its effect on fetal heart development remains unknown. Methods Zebrafish embryos were exposed to celecoxib or other relevant drugs from tailbud stage (10.3-72 h postfertilization). Heart looping and valve formation were examined at different developmental stages by in vivo confocal imaging. In addition, whole mount in situ hybridization was performed to examine drug-induced changes in the expression of heart valve marker genes. Results In celecoxib-treated zebrafish embryos, the heart failed to undergo normal looping and the heart valve was absent, causing serious blood regurgitation. Furthermore, celecoxib treatment disturbed the restricted expression of the heart valve markers bone morphogenetic protein 4 and versican-but not the cardiac chamber markers cardiac myosin light chain 2, ventricular myosin heavy chain, and atrial myosin heavy chain. These defects in heart development were markedly relieved by treatment with the cyclooxygenase-2 downstream product prostaglandin E2, and mimicked by the cyclooxygenase-2 inhibitor NS398, implying that celecoxib-induced heart defects were caused by the inhibition of cyclooxygenase-2 activity. Conclusions These findings provide the first in vivo evidence that celecoxib exposure impairs heart development in zebrafish embryos by inhibiting cyclooxygenase-2 activity.

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