scholarly journals Insights into regeneration from the genome, transcriptome and metagenome analysis of Eisenia fetida

2017 ◽  
Author(s):  
Aksheev Bhambri ◽  
Neeraj Dhaunta ◽  
Surendra Singh Patel ◽  
Mitali Hardikar ◽  
Nagesh Srikakulam ◽  
...  
Keyword(s):  
Eisenia Fetida ◽  
Hox Genes ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Wide Spectrum ◽  
Bacterial Species ◽  
Draft Genome ◽  
Mirna Gene ◽  
Mesenchymal Transition ◽  
Depth Analysis

AbstractEarthworms show a wide spectrum of regenerative potential with certain species like Eisenia fetida capable of regenerating more than two-thirds of their body while other closely related species, such as Paranais litoralis seem to have lost this ability. Earthworms belong to the phylum annelida, in which the genomes of the marine oligochaete Capitella telata, and the freshwater leech Helobdella robusta have been sequenced and studied. The terrestrial annelids, in spite of their ecological relevance and unique biochemical repertoire, are represented by a single rough genome draft of Eisenia fetida (North American isolate), which suggested that extensive duplications have led to a large number of HOX genes in this annelid. Herein, we report the draft genome sequence of Eisenia fetida (Indian isolate), a terrestrial redworm widely used for vermicomposting assembled using short reads and mate-pair reads. An in-depth analysis of the miRNome of the worm, showed that many miRNA gene families have also undergone extensive duplications. Genes for several important proteins such as sialidases and neurotrophins were identified by RNA sequencing of tissue samples. We also used de novo assembled RNA-Seq data to identify genes that are differentially expressed during regeneration, both in the newly regenerating cells and in the adjacent tissue. Sox4, a master regulator of TGF-beta induced epithelial-mesenchymal transition was induced in the newly regenerated tissue. The regeneration of the ventral nerve cord was also accompanied by the induction of nerve growth factor and neurofilament genes. The metagenome of the worm, characterized using 16S rRNA sequencing, revealed the identity of several bacterial species that reside in the nephridia of the worm. Comparison of the bodywall and cocoon metagenomes showed exclusion of hereditary symbionts in the regenerated tissue. In summary, we present extensive genome, transcriptome and metagenome data to establish the transcriptome and metagenome dynamics during regeneration.

scholarly journals EXTH-51. ANTI-INVASIVE EFFICACY AND SURVIVAL BENEFIT OF THE YAP-TEAD INHIBITOR VERTEPORFIN IN PRECLINICAL GLIOBLASTOMA MODELS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii98-ii98
Author(s):  
Anne Marie Barrette ◽  
Alexandros Bouras ◽  
German Nudelman ◽  
Zarmeen Mussa ◽  
Elena Zaslavsky ◽  
...  
Keyword(s):  
Survival Benefit ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Intraperitoneal Administration ◽  
Standard Of Care ◽  
Tumor Burden ◽  
Mesenchymal Transition ◽  
Protein Levels

Abstract Glioblastoma (GBM) remains an incurable disease, in large part due to its malignant infiltrative spread, and current clinical therapy fails to target the invasive nature of tumor cells in disease progression and recurrence. Here, we use the YAP-TEAD inhibitor Verteporfin to target a convergence point for regulating tumor invasion/metastasis and establish the robust anti-invasive therapeutic efficacy of this FDA-approved drug and its survival benefit across several preclinical glioma models. Using patient-derived GBM cells and orthotopic xenograft models (PDX), we show that Verteporfin treatment disrupts YAP/TAZ-TEAD activity and processes related to cell adhesion, migration and epithelial-mesenchymal transition. In-vitro, Verteporfin impairs tumor migration, invasion and motility dynamics. In-vivo, intraperitoneal administration of Verteporfin in mice with orthotopic PDX tumors shows consistent drug accumulation within the brain and decreased infiltrative tumor burden, across three independent experiments. Interestingly, PDX tumors with impaired invasion after Verteporfin treatment downregulate CDH2 and ITGB1 adhesion protein levels within the tumor microenvironment. Finally, Verteporfin treatment confers survival benefit in two independent PDX models: as monotherapy in de-novo GBM and in combination with standard-of-care chemoradiation in recurrent GBM. These findings indicate potential therapeutic value of this FDA-approved drug if repurposed for GBM patients.

scholarly journals Phosphorylation of Serine 11 and Serine 92 as New Positive Regulators of Human Snail1 Function: Potential Involvement of Casein Kinase-2 and the cAMP-activated Kinase Protein Kinase A

2010 ◽  
Vol 21 (2) ◽  
pp. 244-253 ◽  
Author(s):  
Matthew Reid MacPherson ◽  
Patricia Molina ◽  
Serhiy Souchelnytskyi ◽  
Christer Wernstedt ◽  
Jorge Martin-Pérez ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cop9 Signalosome ◽  
Mesenchymal Transition ◽  
Depth Analysis ◽  
Positive Regulators

Snail1 is a major factor for epithelial-mesenchymal transition (EMT), an important event in tumor metastasis and in other pathologies. Snail1 is tightly regulated at transcriptional and posttranscriptional levels. Control of Snail1 protein stability and nuclear export by GSK3β phosphorylation is important for Snail1 functionality. Stabilization mechanisms independent of GSK3β have also been reported, including interaction with LOXL2 or regulation of the COP9 signalosome by inflammatory signals. To get further insights into the role of Snail1 phosphorylation, we have performed an in-depth analysis of in vivo human Snail1 phosphorylation combined with mutational studies. We identify new phosphorylation sites at serines 11, 82, and 92 and confirmed previously suggested phosphorylations at serine 104 and 107. Serines 11 and 92 participate in the control of Snail1 stability and positively regulate Snail1 repressive function and its interaction with mSin3A corepressor. Furthermore, serines 11 and 92 are required for Snail1-mediated EMT and cell viability, respectively. PKA and CK2 have been characterized as the main kinases responsible for in vitro Snail1 phosphorylation at serine 11 and 92, respectively. These results highlight serines 11 and 92 as new players in Snail1 regulation and suggest the participation of CK2 and PKA in the modulation of Snail1 functionality.

scholarly journals Multi-regional characterisation of renal cell carcinoma and microenvironment at single cell resolution

2021 ◽  
Author(s):  
Ruoyan Li ◽  
John R. Ferdinand ◽  
Kevin W. Loudon ◽  
Georgina S. Bowyer ◽  
Lira Mamanova ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Function ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Spatial Location ◽  
De Novo Mutation ◽  
Cellular Interactions ◽  
Sequencing Data ◽  
Mesenchymal Transition ◽  
Multiple Regions

Tumour behaviour is dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. These dependencies were examined through 270,000 single cell transcriptomes and 100 micro-dissected whole exomes obtained from 12 patients with kidney tumours. Tissue was sampled from multiple regions of tumour core, tumour-normal interface, normal surrounding tissues, and peripheral blood. We found the principal spatial location of CD8+ T cell clonotypes largely defined exhaustion state, with clonotypic heterogeneity not explained by somatic intra-tumoural heterogeneity. De novo mutation calling from single cell RNA sequencing data allows us to lineage-trace and infer clonality of cells. We discovered six meta-programmes that distinguish tumour cell function. An epithelial-mesenchymal transition meta-programme, enriched at the tumour-normal interface appears modulated through macrophage expressed IL1B, potentially forming a therapeutic target.

scholarly journals Phenotypic Transition of the Collecting Duct Epithelium in Congenital Urinary Tract Obstruction

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Peter Trnka ◽  
Michael J. Hiatt ◽  
Larissa Ivanova ◽  
Alice F. Tarantal ◽  
Douglas G. Matsell
Keyword(s):  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Urinary Tract Obstruction ◽  
Collecting Duct ◽  
Obstructive Nephropathy ◽  
Primate Model ◽  
Mesenchymal Transition ◽  
Duct Epithelium ◽  
Collecting Duct Epithelium

Epithelial-mesenchymal transition (EMT) has emerged in recent years as an important process in the development of organ fibrosis in many human diseases. Our previous experience in a nonhuman primate model of obstructive nephropathy suggested that EMT of collecting duct epithelium contributes to the development of interstitial fibrosis. In this study we demonstrate for the first time in humans that obstructed fetal collecting duct epithelium undergoes transition to mesenchymal phenotype, characterized by decreased expression of epithelial markers, de novo expression of mesenchymal markers with subsequent loss of cell-cell interaction, disruption of the basement membrane, and increased deposition of extracellular matrix into the expanded interstitium of the obstructed kidney. The results of this study therefore support the previous findings from animal studies and suggest that EMT of the collecting duct epithelium might contribute to the development of interstitial fibrosis in human fetal obstructive nephropathy.

scholarly journals Explanting Is anEx VivoModel of Renal Epithelial-Mesenchymal Transition

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Catherine E. Winbanks ◽  
Ian A. Darby ◽  
Kristen J. Kelynack ◽  
Dodie Pouniotis ◽  
Gavin J. Becker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Ex Vivo ◽  
Rat Kidney ◽  
Smooth Muscle Actin ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Mesenchymal Transition ◽  
Renal Tubulointerstitial Fibrosis

Recognised by theirde novoexpression of alpha-smooth muscle actin (SMA), recruitment of myofibroblasts is key to the pathogenesis of fibrosis in chronic kidney disease. Increasingly, we realise that epithelial-mesenchymal transition (EMT) may be an important source of these cells. In this study we describe a novel model of renal EMT. Rat kidney explants were finely diced on gelatin-coated Petri dishes and cultured in serum-supplemented media. Morphology and immunocytochemistry were used to identify mesenchymal (vimentin+, α-smooth muscle actin (SMA)+, desmin+), epithelial (cytokeratin+), and endothelial (RECA+) cells at various time points. Cell outgrowths were all epithelial in origin (cytokeratin+) at day 3. By day 10, 50 ± 12% (mean ± SE) of cytokeratin+ cells double-labelled for SMA, indicating EMT. Lectin staining established a proximal tubule origin. By day 17, cultures consisted only of myofibroblasts (SMA+/cytokeratin−). Explanting is a reproducibleex vivomodel of EMT. The ability to modify this change in phenotype provides a useful tool to study the regulation and mechanisms of renal tubulointerstitial fibrosis.

CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics

2017 ◽  
Vol 55 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Ting-juan Zhang ◽  
Jing-dong Zhou ◽  
Ji-chun Ma ◽  
Zhao-qun Deng ◽  
Zhen Qian ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Marker Gene ◽  
Transcript Level ◽  
Mesenchymal Transition ◽  
Cell Counts ◽  
Acute Myeloid ◽  
E Cadherin

Abstract Background: Epithelial-mesenchymal transition (EMT) is a critical process which involves in tumor metastasis. As an important EMT marker gene, CDH1 (E-cadherin) expression and its clinical implication in acute myeloid leukemia (AML) remain largely elusive. Methods: Real-time quantitative PCR (RQ-PCR) was carried out to examine CDH1 transcript level in 123 de novo AML patients and 34 controls. Results: Compared with controls, CDH1 was significantly downregulated in AML (p<0.001). The median level of CDH1 expression divided total AML patients into CDH1 low-expressed (CDH11ow) and CDH1 high-expressed (CDH1high) groups. There were no significant differences between the two groups in age, peripheral blood cell counts, complete remission (CR) rate, and the distribution of FAB/WHO subtypes as well as karyotypes/karyotypic classifications (p>0.05). However, CDH11ow group tended to have a higher bone marrow (BM) blasts (p=0.093). The spearman correlation analysis further illustrated a trend towards a negative correlation between CDH1 expression level and BM blasts (r=–0.214, p=0.052). CDH1low group had a tendency towards a lower frequency of N/K-RAS mutations (p=0.094). Furthermore, CDH1low patients had markedly shorter overall survival (OS) time in cytogenetic normal AML (CN-AML) (p=0.019). Both univariate and multivariate analyses confirmed the prognostic value of CDH1 expression in CN-AML patients (p=0.027 and 0.033, respectively). Conclusions: CDH1 downregulation acted as an independent prognostic biomarker in CN-AML patients.

scholarly journals Role of HOXC10 in Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinyong Fang ◽  
Jianjun Wang ◽  
Liangliang Yu ◽  
Wenxia Xu
Keyword(s):  
Hox Genes ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Limb Regeneration ◽  
Morphological Development ◽  
Mesenchymal Transition ◽  
Oncogenic Pathways ◽  
The Status ◽  
Sex Regulation

The HOXC10 gene, a member of the HOX genes family, plays crucial roles in mammalian physiological processes, such as limb morphological development, limb regeneration, and lumbar motor neuron differentiation. HOXC10 is also associated with angiogenesis, fat metabolism, and sex regulation. Additional evidence suggests that HOXC10 dysregulation is closely associated with various tumors. HOXC10 is an important transcription factor that can activate several oncogenic pathways by regulating various target molecules such as ERK, AKT, p65, and epithelial mesenchymal transition-related genes. HOXC10 also induces drug resistance in cancers by promoting the DNA repair pathway. In this review, we summarize HOXC10 gene structure and expression as well as the role of HOXC10 in different human cancer processes. This review will provide insight into the status of HOXC10 research and help identify novel targets for cancer therapy.

scholarly journals Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome

2019 ◽  
Author(s):  
Reham Alharatani ◽  
Athina Ververi ◽  
Ana Beleza-Meireles ◽  
Weizhen Ji ◽  
Emily Mis ◽  
...  
Keyword(s):  
Cleft Palate ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Cell Junctions ◽  
P120 Catenin ◽  
Mesenchymal Transition ◽  
Cardiac Syndrome ◽  
Congenital Cardiac Anomalies ◽  
Wide Range ◽  
Range Of Functions

Abstract:CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signaling. Due to advances in next generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic syndrome (BCD) albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in thirteen participants presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described, and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.

scholarly journals Long-Read Genome Sequencing and Assembly of Leptopilina boulardi: A Specialist Drosophila Parasitoid

2020 ◽  
Vol 10 (5) ◽  
pp. 1485-1494
Author(s):  
Shagufta Khan ◽  
Divya Tej Sowpati ◽  
Arumugam Srinivasan ◽  
Mamilla Soujanya ◽  
Rakesh K. Mishra
Keyword(s):  
Dna Methyltransferase ◽  
Hox Genes ◽  
De Novo ◽  
Draft Genome ◽  
Suitable Model ◽  
Heterochromatin Protein 1 ◽  
Protein Coding ◽  
Long Read ◽  
Trna Methyltransferase ◽  
Relationship Of

Leptopilinaboulardi (Hymenoptera: Figitidae) is a specialist parasitoid of Drosophila. The Drosophila-Leptopilina system has emerged as a suitable model for understanding several aspects of host-parasitoid biology. However, a good quality genome of the wasp counterpart was lacking. Here, we report a whole-genome assembly of L. boulardi to bring it in the scope of the applied and fundamental research on Drosophila parasitoids with access to epigenomics and genome editing tools. The 375Mb draft genome has an N50 of 275Kb with 6315 scaffolds >500bp and encompasses >95% complete BUSCOs. Using a combination of ab-initio and RNA-Seq based methods, 25259 protein-coding genes were predicted and 90% (22729) of them could be annotated with at least one function. We demonstrate the quality of the assembled genome by recapitulating the phylogenetic relationship of L. boulardi with other Hymenopterans. The key developmental regulators like Hox genes and sex determination genes are well conserved in L. boulardi, and so is the basic toolkit for epigenetic regulation. The search for epigenetic regulators has also revealed that L. boulardi genome possesses DNMT1 (maintenance DNA methyltransferase), DNMT2 (tRNA methyltransferase) but lacks the de novo DNA methyltransferase (DNMT3). Also, the heterochromatin protein 1 family appears to have expanded as compared to other hymenopterans. The draft genome of L. boulardi (Lb17) will expedite the research on Drosophila parasitoids. This genome resource and early indication of epigenetic aspects in its specialization make it an interesting system to address a variety of questions on host-parasitoid biology.

scholarly journals Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome

2020 ◽  
Vol 29 (11) ◽  
pp. 1900-1921 ◽  
Author(s):  
Reham Alharatani ◽  
Athina Ververi ◽  
Ana Beleza-Meireles ◽  
Weizhen Ji ◽  
Emily Mis ◽  
...  
Keyword(s):  
Cleft Palate ◽  
De Novo ◽  
Epithelial Mesenchymal Transition ◽  
Cell Junctions ◽  
P120 Catenin ◽  
Mesenchymal Transition ◽  
Cardiac Syndrome ◽  
Congenital Cardiac Anomalies ◽  
Wide Range ◽  
Range Of Functions

Abstract CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell–cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.

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