Dynamics of repair and regeneration of adult zebrafish respiratory gill tissue after cryoinjury.

The study of respiratory tissue damage and repair is critical to understand not only the consequences of respiratory tissue exposure to infectious agents, irritants and toxic chemicals, but also to comprehend the pathogenesis of chronic inflammatory lung diseases. To gain further insights into these processes, we developed a gill cryoinjury model in the adult zebrafish. Time course analysis showed that cryoinjury of the gills triggered an inflammatory response, extensive cell death and collagen deposition at the site of injury. However, the inflammation was rapidly resolved, collagen accumulation dissipated and by 3 weeks after injury the affected gill tissue had begun to regenerate. RNA seq analysis of cryoinjured gills, combined with a comparison of zebrafish heart cryoinjury and caudal fin resection datasets, highlighted the differences and similarities of the transcriptional programmes deployed in response to injury in these three zebrafish models. Comparative RNA seq analysis of cryoinjured zebrafish gills with mouse pulmonary fibrosis datasets also identified target genes, including the understudied FIBIN, as differentially expressed in the two species. Further mining, including of human datasets, suggests that FIBIN may contribute to the successful resolution of tissue damage without fibrosis.

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Correlation of Leaf Damage with Uptake and Translocation of Glyphosate in Velvetleaf (Abutilon theophrasti)

Weed Technology ◽

10.1017/s0890037x00043852 ◽

1998 ◽

Vol 12 (2) ◽

pp. 300-307 ◽

Cited By ~ 19

Author(s):

Paul C. C. Feng ◽

Jan S. Ryerse ◽

R. Douglas Sammons

Keyword(s):

Time Course ◽

Leaf Damage ◽

Minimal Amount ◽

Tissue Necrosis ◽

Short Term ◽

Treated Leaf ◽

Lethal Rate ◽

Extensive Cell Death ◽

Measured Time ◽

Extensive Cell

Uptake and translocation of glyphosate in three commercial formulations were examined in velvetleaf, a dicotyledonous weed that is commonly treated with glyphosate. The formulations included Roundup®(MON 35085), Roundup Ultra, and Touchdown®as sold in Canada. A minimal amount of14C-glyphosate was spiked into a lethal rate of each formulation, and the short-term (3 to 72 h) uptake into the treated leaf and subsequent translocation into the plant were measured. Time-course studies showed very rapid uptake and translocation of glyphosate in the Ultra formulation. In comparison, the uptake and translocation of glyphosate in Touchdown was much slower but continued throughout the 72-h period. Glyphosate in the Roundup formulation showed intermediate uptake and translocation. Tissue necrosis at the application sites of Ultra and Roundup was visible within 24 h after treatment. Examinations using stereo and fluorescence microscopy revealed extensive cell death and tissue disruption. Tissue necrosis from Ultra and Roundup was also observed in blank formulations containing no glyphosate and therefore was likely caused by the surfactants. In contrast, the application sites of Touchdown produced little to no leaf damage. Our results demonstrated a direct correlation between tissue necrosis and rapid rates of glyphosate uptake and translocation.

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EPEN-21. IMPAIRED NEURONAL-GLIAL FATE SPECIFICATION IN PEDIATRIC EPENDYMOMA REVEALED BY SINGLE-CELL RNA-SEQ

Neuro-Oncology ◽

10.1093/neuonc/noaa222.158 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii311-iii312

Author(s):

Bernhard Englinger ◽

Johannes Gojo ◽

Li Jiang ◽

Jens M Hübner ◽

McKenzie L Shaw ◽

...

Keyword(s):

Dna Methylation ◽

Single Cell ◽

Regulatory Networks ◽

Target Genes ◽

Target Identification ◽

Rna Seq ◽

Cell Models ◽

Pediatric Ependymoma ◽

Glial Fate ◽

Anatomic Locations

Abstract Ependymoma represents a heterogeneous disease affecting the entire neuraxis. Extensive molecular profiling efforts have identified molecular ependymoma subgroups based on DNA methylation. However, the intratumoral heterogeneity and developmental origins of these groups are only partially understood, and effective treatments are still lacking for about 50% of patients with high-risk tumors. We interrogated the cellular architecture of ependymoma using single cell/nucleus RNA-sequencing to analyze 24 tumor specimens across major molecular subgroups and anatomic locations. We additionally analyzed ten patient-derived ependymoma cell models and two patient-derived xenografts (PDXs). Interestingly, we identified an analogous cellular hierarchy across all ependymoma groups, originating from undifferentiated neural stem cell-like populations towards different degrees of impaired differentiation states comprising neuronal precursor-like, astro-glial-like, and ependymal-like tumor cells. While prognostically favorable ependymoma groups predominantly harbored differentiated cell populations, aggressive groups were enriched for undifferentiated subpopulations. Projection of transcriptomic signatures onto an independent bulk RNA-seq cohort stratified patient survival even within known molecular groups, thus refining the prognostic power of DNA methylation-based profiling. Furthermore, we identified novel potentially druggable targets including IGF- and FGF-signaling within poorly prognostic transcriptional programs. Ependymoma-derived cell models/PDXs widely recapitulated the transcriptional programs identified within fresh tumors and are leveraged to validate identified target genes in functional follow-up analyses. Taken together, our analyses reveal a developmental hierarchy and transcriptomic context underlying the biologically and clinically distinct behavior of ependymoma groups. The newly characterized cellular states and underlying regulatory networks could serve as basis for future therapeutic target identification and reveal biomarkers for clinical trials.

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SPLICE-q: a Python tool for genome-wide quantification of splicing efficiency

BMC Bioinformatics ◽

10.1186/s12859-021-04282-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Verônica R. de Melo Costa ◽

Julianus Pfeuffer ◽

Annita Louloupi ◽

Ulf A. V. Ørom ◽

Rosario M. Piro

Keyword(s):

Gene Expression ◽

Cancer Progression ◽

Time Course ◽

Progressive Increase ◽

Rna Seq ◽

Transcript Processing ◽

Aberrant Transcript ◽

Genome Wide ◽

Splicing Efficiency ◽

Nascent Rna

Abstract Background Introns are generally removed from primary transcripts to form mature RNA molecules in a post-transcriptional process called splicing. An efficient splicing of primary transcripts is an essential step in gene expression and its misregulation is related to numerous human diseases. Thus, to better understand the dynamics of this process and the perturbations that might be caused by aberrant transcript processing it is important to quantify splicing efficiency. Results Here, we introduce SPLICE-q, a fast and user-friendly Python tool for genome-wide SPLICing Efficiency quantification. It supports studies focusing on the implications of splicing efficiency in transcript processing dynamics. SPLICE-q uses aligned reads from strand-specific RNA-seq to quantify splicing efficiency for each intron individually and allows the user to select different levels of restrictiveness concerning the introns’ overlap with other genomic elements such as exons of other genes. We applied SPLICE-q to globally assess the dynamics of intron excision in yeast and human nascent RNA-seq. We also show its application using total RNA-seq from a patient-matched prostate cancer sample. Conclusions Our analyses illustrate that SPLICE-q is suitable to detect a progressive increase of splicing efficiency throughout a time course of nascent RNA-seq and it might be useful when it comes to understanding cancer progression beyond mere gene expression levels. SPLICE-q is available at: https://github.com/vrmelo/SPLICE-q

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MODL-16. ABEMACICLIB, A SELECTIVE CDK4/6 INHIBITOR, RESTRICTS GROWTH OF PEDIATRIC GLIAL-LINEAGE TUMORS IN VITRO AND IN VIVO

Neuro-Oncology ◽

10.1093/neuonc/noaa222.590 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii414-iii414

Author(s):

Muh-Lii Liang ◽

Tsung-Han Hsieh ◽

Tai-Tong Wong

Keyword(s):

Dna Repair ◽

Therapeutic Strategy ◽

Target Genes ◽

Rna Seq ◽

Downstream Target ◽

Rb Phosphorylation ◽

Glial Lineage

Abstract BACKGROUND Glial-lineage tumors constitute a heterogeneous group of neoplasms, comprising gliomas, oligodendrogliomas, and ependymomas, which account for 40%–50% of all pediatric central nervous system tumors. Advances in modern neuro-oncological therapeutics are aimed at improving neoadjuvant chemotherapy and deferring radiotherapy because radiation exposure may cause long-term side effects on the developing brain in young children. Despite aggressive treatment, more than half the high-grade gliomas (pHGGs) and one-third of ependymomas exhibit recurrence within 2 years of initial treatment. METHODS By using integrated bioinformatics and through experimental validation, we found that at least one gene among CCND1, CDK4, and CDK6 was overexpressed in pHGGs and ependymomas. RESULTS The use of abemaciclib, a highly selective CDK4/6 inhibitor, effectively inhibited cell proliferation and reduced the expression of cell cycle–related and DNA repair–related gene expression, which was determined through RNA-seq analysis. The efficiency of abemaciclib was validated in vitro in pHGGs and ependymoma cells and in vivo by using subcutaneously implanted ependymoma cells from patient-derived xenograft (PDX) in mouse models. Abemaciclib demonstrated the suppression of RB phosphorylation, downstream target genes of E2F, G2M checkpoint, and DNA repair, resulting in tumor suppression. CONCLUSION Abemaciclib showed encouraging results in preclinical pediatric glial-lineage tumors models and represented a potential therapeutic strategy for treating challenging tumors in children.

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Mechanism of protective effect of xuan-bai-cheng-qi decoction on LPS-induced acute lung injury based on an integrated network pharmacology and RNA-sequencing approach

Respiratory Research ◽

10.1186/s12931-021-01781-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Huahe Zhu ◽

Shun Wang ◽

Cong Shan ◽

Xiaoqian Li ◽

Bo Tan ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Rna Sequencing ◽

Target Genes ◽

Mammalian Target Of Rapamycin ◽

Network Pharmacology ◽

Protective Mechanism ◽

Rna Seq ◽

Active Components ◽

Integrated Network

AbstractXuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein–protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Verification experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were down-regulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.

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Pineal gland transcriptomic profiling reveals the differential regulation of lncRNA and mRNA related to prolificacy in STH sheep with two FecB genotypes

BMC Genomic Data ◽

10.1186/s12863-020-00957-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Chunyan Li ◽

Xiaoyun He ◽

Zijun Zhang ◽

Chunhuan Ren ◽

Mingxing Chu

Keyword(s):

Pineal Gland ◽

Expression Pattern ◽

Noncoding Rna ◽

Target Genes ◽

Expression Profiles ◽

Enrichment Analysis ◽

Rna Seq ◽

Important Regulator ◽

Gsh Metabolism ◽

Transcriptome Expression

Abstract Background Long noncoding RNA (lncRNA) has been identified as important regulator in hypothalamic-pituitary-ovarian axis associated with sheep prolificacy. However, little is known of their expression pattern and potential roles in the pineal gland of sheep. Herein, RNA-Seq was used to detect transcriptome expression pattern in pineal gland between follicular phase (FP) and luteal phase (LP) in FecBBB (MM) and FecB++ (ww) STH sheep, respectively, and differentially expressed (DE) lncRNAs and mRNAs associated with reproduction were identified. Results Overall, 135 DE lncRNAs and 1360 DE mRNAs in pineal gland between MM and ww sheep were screened. Wherein, 39 DE lncRNAs and 764 DE mRNAs were identified (FP vs LP) in MM sheep, 96 DE lncRNAs and 596 DE mRNAs were identified (FP vs LP) in ww sheep. Moreover, GO and KEGG enrichment analysis indicated that the targets of DE lncRNAs and DE mRNAs were annotated to multiple biological processes such as phototransduction, circadian rhythm, melanogenesis, GSH metabolism and steroid biosynthesis, which directly or indirectly participate in hormone activities to affect sheep reproductive performance. Additionally, co-expression of lncRNAs-mRNAs and the network construction were performed based on correlation analysis, DE lncRNAs can modulate target genes involved in related pathways to affect sheep fecundity. Specifically, XLOC_466330, XLOC_532771, XLOC_028449 targeting RRM2B and GSTK1, XLOC_391199 targeting STMN1, XLOC_503926 targeting RAG2, XLOC_187711 targeting DLG4 were included. Conclusion All of these differential lncRNAs and mRNAs expression profiles in pineal gland provide a novel resource for elucidating regulatory mechanism underlying STH sheep prolificacy.

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Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ

Nature Communications ◽

10.1038/s41467-021-22544-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Giulia Della Chiara ◽

Federica Gervasoni ◽

Michaela Fakiola ◽

Chiara Godano ◽

Claudia D’Oria ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cell ◽

De Novo ◽

Epigenetic Alterations ◽

Human Colorectal Cancer ◽

Active Chromatin ◽

Extensive Cell Death ◽

Extensive Cell ◽

Pan Cancer ◽

Tumor Maintenance

AbstractCancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human tumors, highlighting a pan-cancer epigenetic rewiring which at single-cell level distinguishes malignant from normal cell populations. YAP/TAZ inhibition in established tumor organoids causes extensive cell death unveiling their essential role in tumor maintenance. This work indicates a common layer of YAP/TAZ-fueled enhancer reprogramming that is key for the cancer cell state and can be exploited for the development of improved therapeutic avenues.

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