scholarly journals Transcriptomic Analysis of Early Stages of Intestinal Regeneration in Holothuria glaberrima

2020 ◽  
Author(s):  
David J. Quispe-Parra ◽  
Joshua G. Medina-Feliciano ◽  
Sebastián Cruz-González ◽  
Humberto Ortiz-Zuazaga ◽  
José E. García-Arrarás
Keyword(s):  
De Novo ◽  
Focal Point ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Regenerative Process ◽  
Pathway Enrichment Analysis ◽  
Cellular Processes ◽  
Early Stages ◽  
Intestinal Regeneration ◽  
Holothuria Glaberrima

AbstractEchinoderms comprise a group of animals with impressive regenerative capabilities. They can replace complex internal organs following injury or autotomy. In holothurians or sea cucumbers, cellular processes of intestinal regeneration have been extensively studied. The molecular machinery behind this faculty, however, remains to be understood. Here we assembled and annotated a de novo transcriptome using RNA-seq data consisting of regenerating and non-regenerating intestinal tissues from the sea cucumber Holothuria glaberrima. Comparisons of differential expression were made using the mesentery as a reference against 24 hour and 3 days regenerating intestine, revealing a large number of differentially expressed transcripts. Gene ontology and pathway enrichment analysis showed evidence of increasing transcriptional activity. Further analysis of transcripts associated with transcription factors revealed diverse expression patterns with mechanisms involving developmental and cancer-related activity that could be related to the regenerative process. Our study demonstrates the broad and diversified gene expression profile during the early stages of the process using the mesentery as the focal point of intestinal regeneration. It also establishes the genes that are the most important candidates in the cellular processes that underlie regenerative responses.

scholarly journals A Roadmap for Intestinal Regeneration

2020 ◽  
Vol 52 ◽  
Author(s):  
David Quispe-Parra ◽  
Griselle Valentín ◽  
José E. García-Arrarás
Keyword(s):  
Molecular Mechanism ◽  
Sea Cucumber ◽  
Regenerative Process ◽  
Research Model ◽  
Functional Studies ◽  
Cellular Processes ◽  
Sequencing Technologies ◽  
Cellular Events ◽  
Intestinal Regeneration ◽  
Holothuria Glaberrima

Regeneration of lost or injured organs is an intriguing process where numerous cellular events take place to form the new structure. Studies of this process during reconstitution of the intestine have been performed in echinoderms, particularly in holothurians. Many cellular events triggered during regeneration have been described using the sea cucumber Holothuria glaberrima as a research model. More recent experiments have targeted the molecular mechanism behind the process, a task that has been eased by the new sequencing technologies now available. In this review we present the studies involving cellular processes and the genes that have been identified to be associated with the early events of gut regeneration. We also present the ongoing efforts to perform functional studies necessary to establish the role(s) of the identified genes. A synopsis of the studies is given with the course of the regenerative process established so far.

scholarly journals Identification of candidate genes controlling chilling tolerance of rice in the cold region at the booting stage by BSA-Seq and RNA-Seq

2020 ◽  
Vol 7 (11) ◽  
pp. 201081
Author(s):  
Zhenhua Guo ◽  
Lijun Cai ◽  
Zhiqiang Chen ◽  
Ruiying Wang ◽  
Lanming Zhang ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Bulked Segregant Analysis ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Chilling Tolerance ◽  
Pathway Enrichment Analysis ◽  
Potential Candidate ◽  
Rice Varieties ◽  
Booting Stage ◽  
F2 Population

Rice is sensitive to low temperatures, specifically at the booting stage. Chilling tolerance of rice is a quantitative trait loci that is governed by multiple genes, and thus, its precise identification through the conventional methods is an arduous task. In this study, we investigated the candidate genes related to chilling tolerance at the booting stage of rice. The F2 population was derived from Longjing25 (chilling-tolerant) and Longjing11 (chilling-sensitive) cross. Two bulked segregant analysis pools were constructed. A 0.82 Mb region containing 98 annotated genes on chromosomes 6 and 9 was recognized as the candidate region associated with chilling tolerance of rice at the booting stage. Transcriptomic analysis of Longjing25 and Longjing11 revealed 50 differentially expressed genes (DEGs) on the candidate intervals. KEGG pathway enrichment analysis of DEGs was performed. Nine pathways were found to be enriched, which contained 10 DEGs. A total of four genes had different expression patterns or levels between Longjing25 and Longjing11. Four out of the 10 DEGs were considered as potential candidate genes for chilling tolerance. This study will assist in the cloning of the candidate genes responsible for chilling tolerance and molecular breeding of rice for the development of chilling-tolerant rice varieties.

scholarly journals Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guoqing Shen ◽  
Xiao Zhang ◽  
Jie Gong ◽  
Yang Wang ◽  
Pengdan Huang ◽  
...  
Keyword(s):  
Procambarus Clarkii ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Apoptosis Pathway ◽  
Pathway Enrichment ◽  
Cellular Processes ◽  
Expression Of Genes ◽  
Muscle Tissues

AbstractEach year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

scholarly journals Integrated genomics analysis highlights important SNPs and genes implicated in moderate-to-severe asthma based on GWAS and eQTL datasets

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhouzhou Dong ◽  
Yunlong Ma ◽  
Hua Zhou ◽  
Linhui Shi ◽  
Gongjie Ye ◽  
...  
Keyword(s):  
Bayesian Analysis ◽  
Severe Asthma ◽  
Antigen Processing ◽  
Association Studies ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Type I ◽  
Genome Wide Association Studies ◽  
Bioinformatics Analyses

Abstract Background Severe asthma is a chronic disease contributing to disproportionate disease morbidity and mortality. From the year of 2007, many genome-wide association studies (GWAS) have documented a large number of asthma-associated genetic variants and related genes. Nevertheless, the molecular mechanism of these identified variants involved in asthma or severe asthma risk remains largely unknown. Methods In the current study, we systematically integrated 3 independent expression quantitative trait loci (eQTL) data (N = 1977) and a large-scale GWAS summary data of moderate-to-severe asthma (N = 30,810) by using the Sherlock Bayesian analysis to identify whether expression-related variants contribute risk to severe asthma. Furthermore, we performed various bioinformatics analyses, including pathway enrichment analysis, PPI network enrichment analysis, in silico permutation analysis, DEG analysis and co-expression analysis, to prioritize important genes associated with severe asthma. Results In the discovery stage, we identified 1129 significant genes associated with moderate-to-severe asthma by using the Sherlock Bayesian analysis. Two hundred twenty-eight genes were prominently replicated by using MAGMA gene-based analysis. These 228 replicated genes were enriched in 17 biological pathways including antigen processing and presentation (Corrected P = 4.30 × 10− 6), type I diabetes mellitus (Corrected P = 7.09 × 10− 5), and asthma (Corrected P = 1.72 × 10− 3). With the use of a series of bioinformatics analyses, we highlighted 11 important genes such as GNGT2, TLR6, and TTC19 as authentic risk genes associated with moderate-to-severe/severe asthma. With respect to GNGT2, there were 3 eSNPs of rs17637472 (PeQTL = 2.98 × 10− 8 and PGWAS = 3.40 × 10− 8), rs11265180 (PeQTL = 6.0 × 10− 6 and PGWAS = 1.99 × 10− 3), and rs1867087 (PeQTL = 1.0 × 10− 4 and PGWAS = 1.84 × 10− 5) identified. In addition, GNGT2 is significantly expressed in severe asthma compared with mild-moderate asthma (P = 0.045), and Gngt2 shows significantly distinct expression patterns between vehicle and various glucocorticoids (Anova P = 1.55 × 10− 6). Conclusions Our current study provides multiple lines of evidence to support that these 11 identified genes as important candidates implicated in the pathogenesis of severe asthma.

scholarly journals Elevated Expression of Mir-130a in t(8,21) AML Reinforces the Aberrant Molecular Program of AML1-ETO

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Gabriela Krivdova ◽  
Veronique Voisin ◽  
Sajid Marhon ◽  
Schoof E Erwin ◽  
Martino Gabra ◽  
...  
Keyword(s):  
Stress Responses ◽  
Functional Significance ◽  
De Novo ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Protein Levels ◽  
The Impact

Background: Deregulation of self-renewal and differentiation programs are central to the pathogenesis of hematologic malignancies. MicroRNAs (miRNAs) represent a large class of post-transcriptional regulators that mediate repression of multiple target mRNAs and are frequently deregulated in acute myeloid leukemia (AML). From our previous in vivo miRNA enforced expression screen in human hematopoietic stem and progenitor cells (HSPC), we identified miR-130a as a regulator of self-renewal and lineage specification. Enforced expression of miR-130a in human cord blood (CB) derived HSPC caused an expansion of HSC, block in erythroid differentiation and abnormal myelopoiesis in xenografts. Thus, we examined miR-130a expression in AML and found miR-130a to be specifically upregulated in t(8,21) AML. The translocation t(8,21) is one of the most common karyotypic abnormalities in AML, accounting up to 10% of all AML cases. The consequence of this translocation is a fusion of AML1 and ETO genes, resulting in a formation of the AML1-ETO (AE) oncofusion protein, which acts as a dominant repressor of the wild type AML1/RUNX1. The ETO moiety mediates the recruitment of the nuclear corepressor (NCoR) and histone deacetylases (HDAC1-3) to block RUNX1 target gene expression. This prevents myeloid maturation, apoptosis and promotes leukemogenesis. Here we investigated the molecular mechanism of miR-130a in t(8,21) AML and how it contributes to the leukemogenesis of this AML subtype. Results: Using the TCGA dataset and our PMCC patient cohort, we identified miR-130a to be upregulated in t(8,21) AML and high miR-130a expression was associated with worse patient overall survival. To interrogate the functional significance of elevated miR-130a in t(8,21) AML, we performed knock-down (KD) experiments in the Kasumi-1 cell line, which represents a well characterized model system for t(8,21) AML. Notably, KD of miR-130a induced a significant reduction in the CD34+ cell population and an increase in differentiated CD11b+CD15+ and pro-apoptotic annexin V+ cells. We next examined the impact of miR-130a KD in CD34+ blasts from primary t(8,21) AML patient samples. In line with our findings in the Kasumi-1 cells, miR-130a KD decreased the proportion of CD34+ cells and increased the proportion of differentiated CD11b+CD15+ blasts. To investigate the effect of miR-130a KD on leukemic engraftment in vivo, we transduced CD34+ blasts from 2 patient samples and transplanted them into NSG-GF mice. miR-130a KD decreased leukemic engraftment and the proportion of transduced cells, corroborating the functional significance of high miR-130a expression in t(8,21) AML. To investigate the mechanistic action of miR-130a, we performed label-free semi-quantitative proteomics in human CB derived HSPC to uncover miR-130a targets. Surprisingly, we found the beta subunit of RUNX1, CBFb, and Transducin Beta Like 1 X-Linked Receptor 1, TBL1XR1, to be among the most repressed targets. TBL1XR1 is a component of the nuclear receptor corepressor (NCoR) complex and is involved in NCoR degradation. Thus, we performed western and immunoprecipitations (IP) assays in Flag-AE Kasumi-1 cells following miR-130a KD to examine changes in the expression of proteins associated with the AE complex. We observed increased expression of CBFβ, TBL1XR1 and CEBPA with miR-130a KD. Notably, miR-130a KD resulted in a dramatic decrease of NCoR protein levels. IP of Flag-AE showed decreased association of CBFβ and NCoR with AE, despite unaltered protein levels of AE. To investigate changes in binding occupancy of Flag-AE after miR-130a KD, we performed Cleavage Under the Targets and Release Using Nuclease (CUT&RUN) assay. Surprisingly, we observed 2-fold gain of AE sites in miR-130a KD sample compared to control. De novo motif enrichment analysis showed loss of motives for ETS and HOX transcription factors known to associate with AE following miR-130a KD. Genomic distribution of the peaks revealed a dramatic shift of AE peaks away from the promoter region to introns in miR-130a KD. Pathway enrichment analysis of the unique peaks gained in miR-130a KD showed stress responses and organelle disassembly, in line with the differentiation phenotype observed with miR-130a KD. Collectively, we uncovered a novel mechanism by which miR-130a reinforces the aberrant AE molecular program by controlling the composition and binding of the AE complex. Disclosures Dick: Bristol-Myers Squibb/Celgene: Research Funding.

The Role of SRMS in Colorectal Cancer by Bioinformatics Analysis

2021 ◽  
Author(s):  
jie Zhang ◽  
Weidong Liu ◽  
Sisi Feng ◽  
Baiyun Zhong
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Receptor Interaction ◽  
Marker Genes ◽  
Pathway Enrichment Analysis ◽  
Cell Marker ◽  
Translational Initiation ◽  
Pathway Enrichment

Abstract Background:Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. Therefore, it may be an important carcinogenic factor whose role in colorectal cancer (CRC) has not been established. Methods: We evaluated the expression patterns of SRMS in CRC using GEPIA, Oncomine and HPA datasets while the association between SRMS and clinicopathological features was analyzed using a UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network establishment and pathway enrichment analysis of the SRMS-associated 33 immunomodulators and 191 immune cell marker genes were performed using the STRING portal. Results: Compared to normal colorectal tissues, SRMS was found to be upregulated in CRC tissues, and was correlated with higher pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. Pathway enrichment analysis of SRMS-associated 33 immunomodulators and 191 immune cell marker genes indicated that they are involved multiple cancer-related pathways. Conclusions: SRMS is a promising prognostic biomarker and a potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating chemokines, IL-17, intestinal immune networks for IgA production, and cytokine-cytokine receptor interaction signaling pathways among others. However, more studies are needed to validate these findings.

scholarly journals Identification and comparison of circular RNAs in preeclampsia

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11299
Author(s):  
Zepeng Ping ◽  
Ling Ai ◽  
Huaxiang Shen ◽  
Xing Zhang ◽  
Huling Jiang ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Gestational Hypertension ◽  
Interaction Analysis ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Circular Rnas ◽  
Pathway Enrichment Analysis ◽  
Sequencing Data ◽  
Mortality And Morbidity ◽  
Specific Syndrome

Background Preeclampsia (PE) is a pregnancy-specific syndrome, belongs to the gestational hypertension diseases category and is considered among the causes of maternal and perinatal mortality and morbidity. However, the pathogenesis of PE is still vague. Methods In the present study, the circular RNA (circRNA) expression patterns of normal pregnant women and PE patients were investigated using whole RNA sequencing. Results A total of 151 differential expressed circRNAs were identified including 121 upregulated and 30 downregulated ones. Functional and pathway enrichment analysis was conducted on the differentially expressed circRNAs using Gene Ontology and KEGG databases. The results of this analysis indicated that several crucial biological processes and pathways were enriched in PE patients. circRNA–microRNA (miRNA) interaction analysis indicated that the reported differentially expresse circRNAs may be associated with some regulatory functions through miRNAs in PE patients. Two ceRNAs networks were constructed according to the targeting relationship between circRNAs/miRNAs and miRNAs/mRNAs. One sub-network contained one upregulated circRNA, four downregulated miRNAs and five upregulated mRNAs, and another sub-network contained 10 downregulated circRNAs, 21 upregulated miRNAs and 15 downregulated mRNAs. Conclusion CircRNA expression patterns have been investigated and this analysis revealed their potential regulatory mechanisms in PE patients. We constructed the ceRNAs (competing endogenous RNA) to reveal the potential molecular roles of dysregulated circRNAs in the PE patients using RNA sequencing data. circRNA_13301 was the only one upregulated circRNA in ceRNA being targeted by four miRNAs.

scholarly journals Transcriptome sequencing and drought resistance gene annotation in Quercus liaotungensis leaves

2021 ◽  
Vol 43 (8) ◽  
Author(s):  
Guobao Wang ◽  
Li Qin
Keyword(s):  
Candidate Genes ◽  
Drought Resistance ◽  
De Novo ◽  
Gene Annotation ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Sequencing Platform ◽  
Drought Avoidance ◽  
Transcriptomic Sequencing ◽  
Genes Encoding

AbstractQ. liaotungensis is an important drought-resistant tree species in Northeast China where the climate is dry and rainless. In this study, we performed a deep transcriptomic sequencing in Q. liaotungensis leaves, including de novo assembly and functional annotation for screening the candidate genes involved in drought avoidance. A total of 25,593 unigenes were obtained from Illumina sequencing platform. According to Gene Ontology annotation and KEGG pathway enrichment analysis, we screened a series of candidate genes encoding SOD, POD, CAT, DREB, MYB, WRKY, bZIP, and NAC from the Q. liaotungensis leaf transcriptome, all of which are potentially involved in drought resistance. The results of this study expanded the genetic resources of Q. liaotungensis and provided a theoretical basis for further exploring the functional gene information of Q. liaotungensis.

scholarly journals Comparative transcriptomics characterized the distinct biosynthetic abilities of terpenoid and paeoniflorin biosynthesis in herbaceous peony strains

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8895
Author(s):  
Baowei Lu ◽  
Fengxia An ◽  
Liangjing Cao ◽  
Qian Gao ◽  
Xuan Wang ◽  
...  
Keyword(s):  
De Novo ◽  
Enrichment Analysis ◽  
Flowering Plant ◽  
Pathway Enrichment Analysis ◽  
Chemical Compositions ◽  
Herbaceous Peony ◽  
Sequencing Experiment ◽  
Pharmaceutical Uses ◽  
Monoterpene Glucoside

The herbaceous peony (Paeonia lactiflora Pall.) is a perennial flowering plant of the Paeoniaceae species that is widely cultivated for medical and ornamental uses. The monoterpene glucoside paeoniflorin and its derivatives are the active compounds of the P. lactiflora roots. However, the gene regulation pathways associated with monoterpene and paeoniflorin biosynthesis in P. lactiflora are still unclear. Here, we selected three genotypes of P. lactiflora with distinct morphologic features and chemical compositions that were a result of long-term reproductive isolation. We performed an RNA-sequencing experiment to profile the transcriptome changes of the shoots and roots. Using de novo assembly analysis, we identified 36,264 unigenes, including 521 genes responsible for encoding transcription factors. We also identified 28,925 unigenes that were differentially expressed in different organs and/or genotypes. Pathway enrichment analysis showed that the P. lactiflora unigenes were significantly overrepresented in several secondary metabolite biosynthesis pathways. We identified and profiled 33 genes responsible for encoding the enzymescontrolling the major catalytic reactions in the terpenoid backbone and in monoterpenoid biosynthesis. Our study identified the candidate genes in the terpenoid biosynthesis pathways, providing useful information for metabolic engineering of P. lactiflora intended for pharmaceutical uses and facilitating the development of strategies to improve marker-assist P. lactiflora in the future.

scholarly journals Retinoic Acid Signaling Is Associated with Cell Proliferation, Muscle Cell Dedifferentiation, and Overall Rudiment Size during Intestinal Regeneration in the Sea Cucumber, Holothuria glaberrima

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 873 ◽  
Author(s):  
Jorge Viera-Vera ◽  
José E. García-Arrarás
Keyword(s):  
Retinoic Acid ◽  
Signaling Pathway ◽  
Retinoic Acid Receptor ◽  
Body Parts ◽  
Cell Dedifferentiation ◽  
Cellular Processes ◽  
Regenerative Response ◽  
Results Of Treatment ◽  
Intestinal Regeneration ◽  
Holothuria Glaberrima

Almost every organism has the ability of repairing damaged tissues or replacing lost and worn out body parts, nevertheless the degree of the response substantially differs between each species. Adult sea cucumbers from the Holothuria glaberrima species can eviscerate various organs and the intestinal system is the first one to regenerate. This process involves the formation of a blastema-like structure that derives from the torn mesentery edges by the intervention of specific cellular processes (e.g., cell dedifferentiation and division). Still, the genetic networks controlling the regenerative response in this model system are just starting to be unraveled. In this work we examined if and how the retinoic acid (RA) signaling pathway is involved in the regenerative response of this deuterostome. We first identified and characterized the holothurian orthologs for short chain dehydrogenase/reductase 7 (SDR7) and aldehyde dehydrogenase family 8A1 (ALDH8A1), two enzymes respectively associated with retinaldehyde and RA anabolism. We then showed that the SDR7 transcript was differentially expressed during specific stages of intestinal regeneration while ALDH8A1 did not show significant differences in regenerating tissues when compared to those of normal (non-eviscerated) organisms. Finally, we investigated the consequences of modulating RA signaling during intestinal regeneration using pharmacological tools. We showed that application of an inhibitor (citral) of the enzyme synthesizing RA or a retinoic acid receptor (RAR) antagonist (LE135) resulted in organisms with a significantly smaller intestinal rudiment when compared to those treated with DMSO (vehicle). The two inhibitors caused a reduction in cell division and cell dedifferentiation in the new regenerate when compared to organisms treated with DMSO. Results of treatment with tazarotene (an RAR agonist) were not significantly different from the control. Taken together, these results suggest that the RA signaling pathway is regulating the cellular processes that are crucial for intestinal regeneration to occur. Thus, RA might be playing a role in echinoderm regeneration that is similar to what has been described in other animal systems.

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