scholarly journals Sexually Dimorphic Transcriptomic Changes of Developing Fetal Brain Reveal Signaling Pathways and Marker Genes of Brain Cells in Domestic Pigs

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2439
Author(s):  
Monica Strawn ◽  
Joao G. N. Moraes ◽  
Timothy J. Safranski ◽  
Susanta K. Behura

In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1037.2-1038
Author(s):  
X. Sun ◽  
S. X. Zhang ◽  
S. Song ◽  
T. Kong ◽  
C. Zheng ◽  
...  

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2311
Author(s):  
Hao Ding ◽  
Yueyue Lin ◽  
Tao Zhang ◽  
Lan Chen ◽  
Genxi Zhang ◽  
...  

The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.


2006 ◽  
Vol 24 (1) ◽  
pp. 45-58 ◽  
Author(s):  
Maria Yolanda Covarrubias ◽  
Rishi L. Khan ◽  
Rajanikanth Vadigepalli ◽  
Jan B. Hoek ◽  
James S. Schwaber

Chronic exposure to alcohol modifies physiological processes in the brain, and the severe symptoms resulting from sudden removal of alcohol from the diet indicate that these modifications are functionally important. We investigated the gene expression patterns in response to chronic alcohol exposure (21–28 wk) in the rat nucleus tractus solitarius (NTS), a brain nucleus with a key integrative role in homeostasis and cardiorespiratory function. Using methods and an experimental design optimized for detecting transcriptional changes less than twofold, we found 575 differentially expressed genes. We tested these genes for significant associations with physiological functions and signaling pathways using Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, respectively. Chronic alcohol exposure resulted in significant NTS gene regulation related to the general processes of synaptic transmission, intracellular signaling, and cation transport as well as specific neuronal functions including plasticity and seizure behavior that could be related to alcohol withdrawal symptoms. The differentially expressed genes were also significantly enriched for enzymes of lipid metabolism, glucose metabolism, oxidative phosphorylation, MAP kinase signaling, and calcium signaling pathways from KEGG. Intriguingly, many of the genes we found to be differentially expressed in the NTS are known to be involved in alcohol-induced oxidative stress and/or cell death. The study provides evidence of very extensive alterations of physiological gene expression in the NTS in the adapted state to chronic alcohol exposure.


2021 ◽  
Author(s):  
◽  
Monica P. Strawn

Two experiments were conducted to investigate molecular regulation that impacts fetal brain development in pigs. In the first experiment (Chapter 2), gene expression was profiled by RNA sequencing (RNA-seq) to examine the whole transcriptome of the male (M) and female (F) fetal brain at gestation day (d) 45, 60 and 90. The analysis showed fewer differentially expressed genes (DEGs) in the brain of male and female fetuses in earlier gestation (d45-d60) when compared to late gestation (d60-d90). The homeobox (HOX) A5 gene that regulates pattern formation in early development was in the top upregulated DEGs between d45 to d60 in fetuses of both sexes. This study also found HOX B5 and D3 genes were in the top upregulated genes between d45 and d60 of the fetal brain of females, but not males. The second experiment (Chapter 3) investigated DNA methylation in pigs. DNA methylation in the fetal brain of both sexes at the same three gestation days was performed by enzymatic methyl sequencing (EM-seq). Hotspots of methylation in specific chromosomal regions were observed in the analysis. The analysis identified 1,475 sites in the pig genome that were methylated in the fetal brain, irrespective of sex, during development. The same sites were methylated in a canonically correlated manner in the blood of the adult stage, both in sows and boars. This is consistent with the Dilman theory of developmental aging (DevAge), which suggests that aging and early development of the brain are regulated by common molecular processes. A comparative analysis (Chapter 4) compared the gene expression patterns in the fetal brain and placenta between pigs and mice. The analysis identified 112 genes that were expressed (mean FPKM > 10) in the fetal brain of both species but not expressed (mean FPKM < 1) in the placenta of either species, and 10 genes that were expressed in the placenta of both species but not expressed in the fetal brain. In-silico analysis of the transcription factor binding sites in the 500 bp of the upstream DNA of these common genes revealed that they were commonly regulated by the RE1 silencing transcription factor (REST), which is a multifaceted transcription factor that acts as a master regulator of neurogenesis as well as controls neural excitation and the aging processes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
S. P. Kashyap ◽  
H. C. Prasanna ◽  
Nishi Kumari ◽  
Pallavi Mishra ◽  
B. Singh

Abstract Soil salinity affects the plant growth and productivity detrimentally, but Solanum chilense, a wild relative of cultivated tomato (Solanum lycopersicum L.), is known to have exceptional salt tolerance. It has precise adaptations against direct exposure to salt stress conditions. Hence, a better understanding of the mechanism to salinity stress tolerance by S. chilense can be accomplished by comprehensive gene expression studies. In this study 1-month-old seedlings of S. chilense and S. lycopersicum were subjected to salinity stress through application of sodium chloride (NaCl) solution. Through RNA-sequencing here we have studied the differences in the gene expression patterns. A total of 386 million clean reads were obtained through RNAseq analysis using the Illumina HiSeq 2000 platform. Clean reads were further assembled de novo into a transcriptome dataset comprising of 514,747 unigenes with N50 length of 578 bp and were further aligned to the public databases. Genebank non-redundant (Nr), Viridiplantae, Gene Ontology (GO), KOG, and KEGG databases classification suggested enrichment of these unigenes in 30 GO categories, 26 KOG, and 127 pathways, respectively. Out of 265,158 genes that were differentially expressed in response to salt treatment, 134,566 and 130,592 genes were significantly up and down-regulated, respectively. Upon placing all the differentially expressed genes (DEG) in known signaling pathways, it was evident that most of the DEGs involved in cytokinin, ethylene, auxin, abscisic acid, gibberellin, and Ca2+ mediated signaling pathways were up-regulated. Furthermore, GO enrichment analysis was performed using REVIGO and up-regulation of multiple genes involved in various biological processes in chilense under salinity were identified. Through pathway analysis of DEGs, “Wnt signaling pathway” was identified as a novel pathway for the response to the salinity stress. Moreover, key genes for salinity tolerance, such as genes encoding proline and arginine metabolism, ROS scavenging system, transporters, osmotic regulation, defense and stress response, homeostasis and transcription factors were not only salt-induced but also showed higher expression in S. chilense as compared to S. lycopersicum. Thus indicating that these genes may have an important role in salinity tolerance in S. chilense. Overall, the results of this study improve our understanding on possible molecular mechanisms underlying salt tolerance in plants in general and tomato in particular.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aliki Xanthopoulou ◽  
Javier Montero-Pau ◽  
Belén Picó ◽  
Panagiotis Boumpas ◽  
Eleni Tsaliki ◽  
...  

Abstract Background Summer squash (Cucurbita pepo: Cucurbitaceae) are a popular horticultural crop for which there is insufficient genomic and transcriptomic information. Gene expression atlases are crucial for the identification of genes expressed in different tissues at various plant developmental stages. Here, we present the first comprehensive gene expression atlas for a summer squash cultivar, including transcripts obtained from seeds, shoots, leaf stem, young and developed leaves, male and female flowers, fruits of seven developmental stages, as well as primary and lateral roots. Results In total, 27,868 genes and 2352 novel transcripts were annotated from these 16 tissues, with over 18,000 genes common to all tissue groups. Of these, 3812 were identified as housekeeping genes, half of which assigned to known gene ontologies. Flowers, seeds, and young fruits had the largest number of specific genes, whilst intermediate-age fruits the fewest. There also were genes that were differentially expressed in the various tissues, the male flower being the tissue with the most differentially expressed genes in pair-wise comparisons with the remaining tissues, and the leaf stem the least. The largest expression change during fruit development was early on, from female flower to fruit two days after pollination. A weighted correlation network analysis performed on the global gene expression dataset assigned 25,413 genes to 24 coexpression groups, and some of these groups exhibited strong tissue specificity. Conclusions These findings enrich our understanding about the transcriptomic events associated with summer squash development and ripening. This comprehensive gene expression atlas is expected not only to provide a global view of gene expression patterns in all major tissues in C. pepo but to also serve as a valuable resource for functional genomics and gene discovery in Cucurbitaceae.


2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.


Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 82
Author(s):  
Yunxiao Wei ◽  
Guoliang Li ◽  
Shujiang Zhang ◽  
Shifan Zhang ◽  
Hui Zhang ◽  
...  

Allopolyploidy is an evolutionary and mechanistically intriguing process involving the reconciliation of two or more sets of diverged genomes and regulatory interactions, resulting in new phenotypes. In this study, we explored the gene expression patterns of eight F2 synthetic Brassica napus using RNA sequencing. We found that B. napus allopolyploid formation was accompanied by extensive changes in gene expression. A comparison between F2 and the parent shows a certain proportion of differentially expressed genes (DEG) and activation\silent gene, and the two genomes (female parent (AA)\male parent (CC) genomes) showed significant differences in response to whole-genome duplication (WGD); non-additively expressed genes represented a small portion, while Gene Ontology (GO) enrichment analysis showed that it played an important role in responding to WGD. Besides, genome-wide expression level dominance (ELD) was biased toward the AA genome, and the parental expression pattern of most genes showed a high degree of conservation. Moreover, gene expression showed differences among eight individuals and was consistent with the results of a cluster analysis of traits. Furthermore, the differential expression of waxy synthetic pathways and flowering pathway genes could explain the performance of traits. Collectively, gene expression of the newly formed allopolyploid changed dramatically, and this was different among the selfing offspring, which could be a prominent cause of the trait separation. Our data provide novel insights into the relationship between the expression of differentially expressed genes and trait segregation and provide clues into the evolution of allopolyploids.


2004 ◽  
Vol 17 (1) ◽  
pp. 11-20 ◽  
Author(s):  
David M. Mutch ◽  
Pascale Anderle ◽  
Muriel Fiaux ◽  
Robert Mansourian ◽  
Karine Vidal ◽  
...  

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.


2021 ◽  
Author(s):  
Shuo Chen ◽  
Yuzhou Chang ◽  
Liangping Li ◽  
Diana Acosta ◽  
Cody Morrison ◽  
...  

Alzheimer's disease (AD) is pathologically characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles (tau aggregates), and alterations in microglia, astrocytes and oligodendrocytes. The mesial temporal lobe is a vulnerable brain region in early AD; however, little is known about the transcriptome-scale gene expression in this region and its relation to AD pathology. Here we use the 10x Genomics Visium platform in combination with co-immunofluorescence staining of AD-associated pathological markers to define the spatial topography of gene expression in the middle temporal gyrus (MTG) from both early AD and age- and gender-matched control cases. We identify unique marker genes for six cortical layers and the adjacent white matter as well as gene expression patterns and alterations that showcase unique gene signatures and pathways associated with a range of AD pathology. Also, gene co-expression analyses of differentially expressed genes (DEGs) between AD and controls reveal four unique gene modules, which significantly change their co-expression patterns in the presence of variations of AD pathology. Furthermore, we validate the changes of key representative DEGs that are associated with AD pathology in neurons, microglia, astrocytes and oligodendrocytes using single-molecule fluorescent in situ hybridization. In summary, we provide a rich resource for the spatial transcriptomic profile of the human MTG, which will contribute to our understanding of the complex architecture and AD pathology of this vulnerable brain region.


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