Transcriptome Analysis Reveals Candidate Genes Regulating the Skin and Hair Diversity of Xinji Fine-Wool Sheep and Tan Sheep

The hair follicle is a complex mini-organ in the skin that undergoes organ induction, morphogenesis, and regeneration. However, the accurate molecular mechanism of skin and hair diversity regulation is still elusive. The sheep is an animal model that can be used to further explore the mechanisms of skin and hair diversity. In this study, we carried out a transcriptomic analysis of the mRNA expression in the skin of Xinji fine-wool sheep at different growth stages (3 and 12 months old) and 12-month-old Tan sheep and explored the transcripts’ relationship with hair follicle growth. A total of 1327 mRNAs and 67 transcription factors were identified to be differentially expressed in the different breeds and during different periods of skin development. The differentially expressed genes were enriched in GO terms represented by system development, multicellular organism development, animal organ development, and skin development, and three KEGG pathways typified those governing differences in skin structure. Combining protein–protein interaction networks of skin development (GO:0043588) and functional annotation, nine important candidate genes, namely, LAMA5, OVOL1, SRF, DHCR24, NGFR, SMO, CDSN, HOXC13, and KDF1, and many core genes with minor effects were confirmed to be associated with hair follicle development. Furthermore, members of the zf-C2H2 and homeobox transcription factor families, which were identified to play a crucial role in producing finer and denser wool, were mainly upregulated in 12-month-old Xinji fine-wool sheep when compared with expression in 12-month-old Tan sheep and 3-month-old Xinji fine-wool sheep. This study revealed the major–minor gene interactions in the developmental pathway and provided ideas for an in-depth understanding of the genetic structure and gene regulation in the skin/hair growth process.

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Integrative analysis of Iso-Seq and RNA-seq data reveals transcriptome complexity and differentially expressed transcripts in sheep tail fat

PeerJ ◽

10.7717/peerj.12454 ◽

2021 ◽

Vol 9 ◽

pp. e12454

Author(s):

Zehu Yuan ◽

Ling Ge ◽

Jingyi Sun ◽

Weibo Zhang ◽

Shanhe Wang ◽

...

Keyword(s):

Candidate Genes ◽

Messenger Rna ◽

Molecular Mechanisms ◽

Alternative Polyadenylation ◽

Fat Deposition ◽

Differentially Expressed ◽

Rna Seq ◽

Protein Protein Interaction ◽

Kegg Pathways ◽

Novel Transcripts

Background Nowadays, both customers and producers prefer thin-tailed fat sheep. To effectively breed for this phenotype, it is important to identify candidate genes and uncover the genetic mechanism related to tail fat deposition in sheep. Accumulating evidence suggesting that post-transcriptional modification events of precursor-messenger RNA (pre-mRNA), including alternative splicing (AS) and alternative polyadenylation (APA), may regulate tail fat deposition in sheep. Differentially expressed transcripts (DETs) analysis is a way to identify candidate genes related to tail fat deposition. However, due to the technological limitation, post-transcriptional modification events in the tail fat of sheep and DETs between thin-tailed and fat-tailed sheep remains unclear. Methods In the present study, we applied pooled PacBio isoform sequencing (Iso-Seq) to generate transcriptomic data of tail fat tissue from six sheep (three thin-tailed sheep and three fat-tailed sheep). By comparing with reference genome, potential gene loci and novel transcripts were identified. Post-transcriptional modification events, including AS and APA, and lncRNA in sheep tail fat were uncovered using pooled Iso-Seq data. Combining Iso-Seq data with six RNA-sequencing (RNA-Seq) data, DETs between thin- and fat-tailed sheep were identified. Protein protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were implemented to investigate the potential functions of DETs. Results In the present study, we revealed the transcriptomic complexity of the tail fat of sheep, result in 9,001 potential novel gene loci, 17,834 AS events, 5,791 APA events, and 3,764 lncRNAs. Combining Iso-Seq data with RNA-Seq data, we identified hundreds of DETs between thin- and fat-tailed sheep. Among them, 21 differentially expressed lncRNAs, such as ENSOART00020036299, ENSOART00020033641, ENSOART00020024562, ENSOART00020003848 and 9.53.1 may regulate tail fat deposition. Many novel transcripts were identified as DETs, including 15.527.13 (DGAT2), 13.624.23 (ACSS2), 11.689.28 (ACLY), 11.689.18 (ACLY), 11.689.14 (ACLY), 11.660.12 (ACLY), 22.289.6 (SCD), 22.289.3 (SCD) and 22.289.14 (SCD). Most of the identified DETs have been enriched in GO and KEGG pathways related to extracellular matrix (ECM). Our result revealed the transcriptome complexity and identified many candidate transcripts in tail fat, which could enhance the understanding of molecular mechanisms behind tail fat deposition.

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The Wave complex controls epidermal morphogenesis and proliferation by suppressing Wnt–Sox9 signaling

The Journal of Cell Biology ◽

10.1083/jcb.201807216 ◽

2019 ◽

Vol 218 (4) ◽

pp. 1390-1406 ◽

Cited By ~ 4

Author(s):

Jonathan Cohen ◽

Shaul Raviv ◽

Orit Adir ◽

Krishnanand Padmanabhan ◽

Arad Soffer ◽

...

Keyword(s):

Hair Follicle ◽

Loss Of Function ◽

Filamentous Actin ◽

Follicle Growth ◽

Cell Specification ◽

Skin Development ◽

Interfollicular Epidermis ◽

Hair Follicle Growth ◽

Spatiotemporal Control ◽

Wave Complex

Development of the skin epidermis requires tight spatiotemporal control over the activity of several signaling pathways; however, the mechanisms that orchestrate these events remain poorly understood. Here, we identify a key role for the Wave complex proteins ABI1 and Wave2 in regulating signals that control epidermal shape and growth. In utero RNAi-mediated silencing of Abi1 or Wasf2 induced cellular hyperproliferation and defects in architecture of the interfollicular epidermis (IFE) and delayed hair follicle growth. Unexpectedly, SOX9, a hair follicle growth regulator, was aberrantly expressed throughout the IFE of the mutant embryos, and its forced overexpression mimicked the Wave complex loss-of-function phenotype. Moreover, Wnt signaling, which regulates SOX9+ cell specification, was up-regulated in Wave complex loss-of-function IFE. Importantly, we show that the Wave complex regulates filamentous actin content and that a decrease in actin levels is sufficient to elevate Wnt/β-catenin signaling. Our results identify a novel role for Wave complex– and actin-regulated signaling via Wnt and SOX9 in skin development.

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Skin Transcriptome Analysis Identifies the Key Genes Underlying Fur Development in Chinese Tan Sheep in the Birth and Er-mao Periods

10.21203/rs.3.rs-27729/v1 ◽

2020 ◽

Author(s):

ya chao Li ◽

Ma Yue Hui ◽

Qin Ma ◽

Wei Ding ◽

Yong Hong Chen ◽

...

Keyword(s):

Hair Follicle ◽

Differentially Expressed Gene ◽

Immunohistochemical Analysis ◽

Differentially Expressed ◽

P Value ◽

Follicle Development ◽

Rna Seq ◽

Kegg Analysis ◽

Tan Sheep ◽

Hair Follicle Development

Abstract BackgroundHairfollicle development in Tan sheepdiffers significantly between the birth and Er-mao periods, but the underlying molecular mechanism is still unclear.MethodsWe profiled the skin transcriptomes of Tan sheepinthe birth and Er-mao periods via RNA-seq technology. TheTan sheep examined consisted ofthree sheep inthe birth period and threesheep inthe Er-mao period. ResultsA total of 364 differentially expressed genes (DEGs) in the skin of Tan sheepbetweenthe birth period and the Er-mao period were identified, among which 168 were upregulated and 196 were downregulated. Interestingly, the FOS proto-oncogene(FOS)(fold change=22.67, P value=2.15*10^-44)was the most significantly differentially expressed gene. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the FOS gene was significantly enriched in the signaling pathway related to hair follicle development. Immunohistochemical analysis showed that the FOS gene was expressed in the skin of Chinese Tan sheep at the birth and Er-mao periods,with abnormally high expression in the Er-mao period. Conclusions Our findings suggest that the FOS gene promotes hair follicle development in Tan sheep.

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Identification and profiling of microRNA between back and belly Skin in Rex rabbits (Oryctolagus cuniculus)

World Rabbit Science ◽

10.4995/wrs.2018.7058 ◽

2018 ◽

Vol 26 (2) ◽

pp. 179 ◽

Cited By ~ 1

Author(s):

Bohao Zhao ◽

Yang Chen ◽

Lin Mu ◽

Shuaishuai Hu ◽

Xinsheng Wu

Keyword(s):

Hair Follicle ◽

Target Genes ◽

Osteoclast Differentiation ◽

Signalling Pathway ◽

Functional Enrichment ◽

Differentially Expressed ◽

Keratinocyte Differentiation ◽

Signalling Pathways ◽

Skin Development ◽

Candidate Mirnas

Skin is an important trait for Rex rabbits and skin development is influenced by many processes, including hair follicle cycling, keratinocyte differentiation and formation of coat colour and skin morphogenesis. We identified differentially expressed microRNAs (miRNAs) between the back and belly skin in Rex rabbits. In total, 211 miRNAs (90 upregulated miRNAs and 121 downregulated miRNAs) were identified with a |log<sub>2</sub> (fold change)|>1 and <em>P</em>-value<0.05. Using target gene prediction for the miRNAs, differentially expressed predicted target genes were identified and the functional enrichment and signalling pathways of these target genes were processed to reveal their biological functions. A number of differentially expressed miRNAs were found to be involved in regulation of the cell cycle, skin epithelium differentiation, keratinocyte proliferation, hair follicle development and melanogenesis. In addition, target genes regulated by miRNAs play key roles in the activities of the Hedgehog signalling pathway, Wnt signalling pathway, Osteoclast differentiation and MAPK pathway, revealing mechanisms of skin development. Nine candidate miRNAs and 5 predicted target genes were selected for verification of their expression by quantitative reverse transcription polymerase chain reaction. A regulation network of miRNA and their target genes was constructed by analysing the GO enrichment and signalling pathways. Further studies should be carried out to validate the regulatory relationships between candidate miRNAs and their target genes.

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Aberrantly methylated-differentially genes and pathways among Iranian patients with colorectal cancer

Cancer Cell International ◽

10.1186/s12935-021-02053-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mahla Ghorbani ◽

Marjan Azghandi ◽

Mohammad Amin Kerachian

Keyword(s):

Colorectal Cancer ◽

Candidate Genes ◽

Interaction Network ◽

Gene Expression Omnibus ◽

P Value ◽

Gene Methylation ◽

Protein Protein Interaction ◽

Kegg Pathways ◽

Differentially Methylated Genes ◽

Methylation Profiling

Abstract Background Methylation plays an important role in colorectal cancer (CRC) pathogenesis. The goal of this study was to identify aberrantly differentially methylated genes (DMGs) and pathways through bioinformatics analysis among Iranian CRC patients using Methylation Next Generation Sequencing. Methods This study has integrated results of SureSelectXT Methyl-Seq Target with the potential key candidate genes and pathways in CRC. Six CRC and six samples of normal colon were integrated and deeply analyzed. In addition to this gene methylation profiling, several other gene methylation profiling datasets were obtained from Gene Expression Omnibus (GEO) and TCGA datasets. DMGs were sorted and candidate genes and enrichment pathways were analyzed. DMGs-associated protein–protein interaction network (PPI) was constructed based on the STRING online database. Results Totally, 320 genes were detected as common genes between our patients and selected GEO and TCGA datasets from the Agilent SureSelect analysis with selecting criteria of p-value < 0.05 and FC ≥ 1.5. DMGs were identified from hyper-DMGs PPI network complex and 10 KEGG pathways were identified. The most important modules were extracted from MCODE, as most of the corresponding genes were involved in cellular process and protein binding. Conclusions Hub genes including WNT2, SFRP2, ZNF726 and BMP2 were suggested as potentially diagnostic and therapeutic targets for CRC.

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BMP signaling in the control of skin development and hair follicle growth

Differentiation ◽

10.1111/j.1432-0436.2004.07209005.x ◽

2004 ◽

Vol 72 (9-10) ◽

pp. 512-526 ◽

Cited By ~ 109

Author(s):

Vladimir A. Botchkarev ◽

Andreij A. Sharov

Keyword(s):

Hair Follicle ◽

Bmp Signaling ◽

Follicle Growth ◽

Skin Development ◽

Hair Follicle Growth

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Identification of Differentially Expressed Genes Associated With Precocious Puberty by Suppression Subtractive Hybridization in Goat Pituitary Tissues

10.21203/rs.3.rs-113865/v1 ◽

2020 ◽

Author(s):

Yufang Liu ◽

Guiling Cao ◽

Yujing Xie ◽

Mingxing Chu

Keyword(s):

Differentially Expressed Genes ◽

Suppression Subtractive Hybridization ◽

Precocious Puberty ◽

Subtractive Hybridization ◽

Differentially Expressed ◽

Growth Stages ◽

Kegg Pathways ◽

Oocyte Meiosis ◽

Go Terms ◽

Different Growth Stages

Abstract Background Our study aimed to identify genes related to precocious puberty expressed in the pituitary of different growth stages goats using suppression subtractive hybridization (SSH) screening. Pituitary tissues at 30 day and 90 day and 180 day growth stages of Jining gray goats and Liaoning cashmere goats were used in this study. To identify differentially expressed genes in the pituitary tissues, mRNA from these tissues was extracted and SSH libraries were constructed for screening (API, EPI and BPI groups). ResultsA total of 60, 49 and 58 differently expression genes were annotation in the database. 222 Gene Ontology (GO) terms and 75 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were matched to those genes. Most differentially expressed genes (DEGs) related to the GO terms “structural constituent of ribosome”, “translation” and “GTP binding” were significantly enriched while numerous DEGs related to the Jak-STAT signaling and oocyte meiosis pathways were also significantly enriched. Candidate genes to be involved in precocious puberty and sexual development were retrieved from the SSH libraries. These related genes were discussed taking into account whether they were expressed in different growth stages of pituitary tissues, and of which them influenced the hypothalamic-pituitary-gonadal (HPG) axis. ConclusionsInteresting findings about precocious puberty related genes from an evolutionary perspective (such as PRLP0, EIF5A and YWHAH) and for putative future goats breeding applications are reported here. We provide a valuable dataset that will facilitate further research into the reproductive biology of goats.

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Proteomic analysis of coarse and fine skin tissues of Liaoning cashmere goat

10.1101/2021.09.20.461155 ◽

2021 ◽

Author(s):

Zhixian Bai

Keyword(s):

Differentially Expressed ◽

Differentially Expressed Proteins ◽

Cashmere Goat ◽

Protein Protein Interaction ◽

Kegg Pathways ◽

Growing Period ◽

Tandem Mass Tag ◽

A Cell ◽

Cashmere Goats ◽

Liaoning Cashmere Goat

Proteomics is the study of all proteins expressed by a cell or even an organism. However, knowledge of proteins that regulate the fineness of cashmere is limited. Liaoning Cashmere goat (LCG) is a valuable genetic resource of China. The skin samples of Liaoning cashmere goats during the growing period were collected performed Tandem Mass Tag (TMT) method and identified 117 differentially expressed proteins in CT_LCG (course type) and FT_LCG (fine type). To verify protein genes differentially expressed in LCG, we performed PRM validation on three candidate proteins (ALB, SDC1 and ITGB4) in CT-LCG and FT-LCG. Furthermore, primary metabolic process and lysosome are most enriched in the GO and KEGG pathways, respectively. In addition, we also derived a protein-protein interaction (PPI) regulatory network from the perspective of bioinformatics. This study sought to elucidate the molecular mechanism of differential proteins regulating cashmere fineness of Liaoning cashmere goats by using TMT quantitative proteomics analysis. Differentially expressed proteins ALB and SDC1 may regulate cashmere fineness, ITGB4 can be further studied as a promising protein. Theycan be used as key genes to lay a foundation for the study of cashmere fineness of Liaoning cashmere goats.

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Integrated MicroRNA–mRNA Analyses of Distinct Expression Profiles in Hyperoxia-Induced Bronchopulmonary Dysplasia in Neonatal Mice

American Journal of Perinatology ◽

10.1055/s-0041-1726124 ◽

2021 ◽

Author(s):

Chengqiang Wang ◽

Sheng Zhang ◽

Lina Zhu ◽

Jun Duan ◽

Bo Huang ◽

...

Keyword(s):

Bronchopulmonary Dysplasia ◽

Regulatory Network ◽

Expression Profiles ◽

Differentially Expressed ◽

Preterm Neonates ◽

Air Exposure ◽

Ecm Remodeling ◽

Protein Protein Interaction ◽

Kegg Pathways ◽

Go Terms

Objective Bronchopulmonary dysplasia (BPD) is a common chronic lung disease of preterm neonates; the underlying pathogenesis is not fully understood. Recent studies suggested microRNAs (miRNAs) may be involved in BPD. Study Design miRNA and mRNA microarrays were performed to analyze the expression profiles of miRNA and mRNA in BPD and control lung tissues after oxygen and air exposure on day 21. Bioinformatics methods, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were performed to predict the potential functions of differentially expressed genes. Then, miRNA–mRNA regulatory network was constructed by protein–protein interaction (PPI) data and TarBase data. Results Our results showed that a total of 192 differentially expressed miRNAs (74 downregulated and 118 upregulated) and 1,225 differentially expressed mRNAs (479 downregulated and 746 upregulated) were identified between BPD mice and normoxia-control mice. GO and KEGG analysis showed that for downregulated genes, the top significant enriched GO terms and KEGG pathways were both mainly related to immune and inflammation processes; for upregulated genes, the top significant enriched GO terms and KEGG pathways were both mainly related to extracellular matrix (ECM) remodeling. PPI network and miRNA–mRNA regulatory network construction revealed that the key genes and pathways associated with inflammation and immune regulation. Conclusion Our findings revealed the integrated miRNA–mRNA data of distinct expression profiles in hyperoxia-induced BPD mice, and may provide some clues of the potential biomarkers for BPD, and provide novel insights into the development of new promising biomarkers for the treatment of BPD. Key Points

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Comprehensive analyses to identify LINC02310 as an enhancer in lung adenocarcinoma

10.21203/rs.3.rs-18710/v1 ◽

2020 ◽

Author(s):

Wenyuan Zhao ◽

Jun Wang ◽

Qingxi Luo ◽

Wei Peng ◽

Bin Li ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Clinical Analysis ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Expression Data ◽

Protein Protein Interaction ◽

Kegg Pathways ◽

Cancer Genome Atlas ◽

Non Coding Rnas ◽

Go Terms

Abstract Lung adenocarcinoma (LADC) is a major subtype of non-small cell lung cancer (NSCLC) and has one of the highest mortality rates. An increasing number of long non-coding RNAs (lncRNAs) were reported to be associated with the occurrence and progression of LADC. In order to find potential biomarkers for LADC therapies among lncRNAs, 2431 differentially expressed lncRNAs (DElncRNAs) over LADC and adjacent normal samples were identified from The Cancer Genome Atlas (TCGA) expression data. Lnc-YARS2-5, lnc-NPR3-2 and LINC02310, which were the top-3 significant DElncRNAs related to overall survival, were selected for further analysis. Their overexpression indicated poor prognostic. PCR experimental results also showed that they were mainly up-regulated in the LADC tissues from Xiangya Hospital. Clinical analysis of these cases suggested that LINC02310 was significantly correlated with TNM-stage and T-stage, which was further validated by the clinical analysis based on TCGA. Reasonably, we assumed that LINC02310 acted as an enhancer in LADC, which was demonstrated by CCK-8 assay and colony formation assay. Moreover, 3 targeted miRNAs of LINC02310 and 414 downstream differentially expressed mRNAs (DEmRNAs) were predicted. The competing endogenous RNA (ceRNA) regulatory network was constructed with LINC02310, 3 miRNAs and 113 DEmRNAs involved. The downstream mRNAs were then enriched in 405 GO terms and 11 KEGG pathways, which revealed their potential functions and mechanisms. The protein-protein interaction (PPI) network showed the relationships between the downstream mRNAs. In conclusion, this study verified LINC02310 as an enhancer in LADC and conducted comprehensive analyses on its target miRNAs and downstream mRNAs.

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