scholarly journals Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuezhen Tian ◽  
Xuemei Yang ◽  
Jianwen Du ◽  
Weidan Zeng ◽  
Weiwei Wu ◽  
...  

Hair follicle growth and development are a complex and long-term physiological process, which is regulated by a variety of physical factors and signal pathways. Increasing the understanding of the epigenetic regulation and function of candidate genes related to hair follicle development will help to better understand the molecular regulatory mechanisms of hair follicle development. In this study, the methylated DNA immunoprecipitation sequencing (MeDIP-seq) was used to obtain the genome-wide methylation map of the hair follicular development of Super Merino sheep in six stages (fetal skin tissue at 65d, 85d, 105d, 135d, 7d, and 30d after birth). Combined with the results of previous RNA-sequencing, 65 genes were screened out that were both differential methylation and differential expression, including EDN1, LAMC2, NR1D1, RORB, MyOZ3, and WNT2 gene. Differential methylation genes were enriched in Wnt, TNF, TGF-beta, and other signaling pathways related to hair follicle development. The bisulfite sequencing PCR results and MeDIP-seq were basically consistent, indicating that the sequencing results were accurate. As a key gene in the Wnt signaling pathway, both differential methylation and expression gene identified by MeDIP-seq and RNA-seq, further exploration of the function of WNT2 gene revealed that the DNA methylation of exon 5 (CpG11 site) promoted the expression of WNT2 gene. The overexpression vector of lentivirus pLEX-MCS-WNT2 was constructed, and WNT2 gene effectively promoted the proliferation of sheep skin fibroblasts. The results showed that WNT2 gene could promote the growth and development of skin and hair follicles. The results of this study will provide a theoretical basis for further research on sheep hair follicle development and gene regulation mechanisms.

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243507
Author(s):  
Zhihong Wu ◽  
Erhan Hai ◽  
Zhengyang Di ◽  
Rong Ma ◽  
Fangzheng Shang ◽  
...  

Objective Mature hair follicles represent an important stage of hair follicle development, which determines the stability of hair follicle structure and its ability to enter the hair cycle. Here, we used weighted gene co-expression network analysis (WGCNA) to identify hub genes of mature skin and hair follicles in Inner Mongolian cashmere goats. Methods We used transcriptome sequencing data for the skin of Inner Mongolian cashmere goats from fetal days 45–135 days, and divided the co expressed genes into different modules by WGCNA. Characteristic values were used to screen out modules that were highly expressed in mature skin follicles. Module hub genes were then selected based on the correlation coefficients between the gene and module eigenvalue, gene connectivity, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The results were confirmed by quantitative polymerase chain reaction (qPCR). Results Ten modules were successfully defined, of which one, with a total of 3166 genes, was selected as a specific module through sample and gene expression pattern analyses. A total of 584 candidate hub genes in the module were screened by the correlation coefficients between the genes and module eigenvalue and gene connectivity. Finally, GO/KEGG functional enrichment analyses detected WNT10A as a key gene in the development and maturation of skin hair follicles in fetal Inner Mongolian cashmere goats. qPCR showed that the expression trends of 13 genes from seven fetal skin samples were consistent with the sequencing results, indicating that the sequencing results were reliable.n


2005 ◽  
Vol 25 (5) ◽  
pp. 1696-1712 ◽  
Author(s):  
Nicolas Di-Poï ◽  
Chuan Young Ng ◽  
Nguan Soon Tan ◽  
Zhongzhou Yang ◽  
Brian A. Hemmings ◽  
...  

ABSTRACT Hair follicle morphogenesis depends on a delicate balance between cell proliferation and apoptosis, which involves epithelium-mesenchyme interactions. We show that peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) and Akt1 are highly expressed in follicular keratinocytes throughout hair follicle development. Interestingly, PPARβ/δ- and Akt1-deficient mice exhibit similar retardation of postnatal hair follicle morphogenesis, particularly at the hair peg stage, revealing a new important function for both factors in the growth of early hair follicles. We demonstrate that a time-regulated activation of the PPARβ/δ protein in follicular keratinocytes involves the up-regulation of the cyclooxygenase 2 enzyme by a mesenchymal paracrine factor, the hepatocyte growth factor. Subsequent PPARβ/δ-mediated temporal activation of the antiapoptotic Akt1 pathway in vivo protects keratinocytes from hair pegs against apoptosis, which is required for normal hair follicle development. Together, these results demonstrate that epithelium-mesenchyme interactions in the skin regulate the activity of PPARβ/δ during hair follicle development via the control of ligand production and provide important new insights into the molecular biology of hair growth.


2021 ◽  
Vol 12 ◽  
Author(s):  
Junyang Liu ◽  
Qing Mu ◽  
Zhihong Liu ◽  
Yan Wang ◽  
Jiasen Liu ◽  
...  

Secondary hair follicle growth in cashmere goats has seasonal cycle changes, and melatonin (MT) has a regulatory effect on the cashmere growth cycle. In this study, the growth length of cashmere was measured by implanting MT in live cashmere goats. The results indicated that the continuous implantation of MT promoted cashmere to enter the anagen 2 months earlier and induce secondary hair follicle development. HE staining of skin tissues showed that the number of secondary hair follicles in the MT-implanted goats was significantly higher than that in the control goats (P < 0.05). Transcriptome sequencing of the skin tissue of cashmere goats was used to identify differentially expressed genes: 532 in February, 641 in October, and 305 in December. Fluorescence quantitative PCR and Western blotting results showed that MT had a significant effect on the expression of Wnt10b, β-catenin, and proteins in the skin tissue of Inner Mongolia cashmere goats. This finding suggested that MT alters the cycle of secondary hair follicle development by changing the expression of related genes. This research lays the foundation for further study on the mechanism by which MT regulates cashmere growth.


2019 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)|>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7167 ◽  
Author(s):  
Bo Zhai ◽  
Lichun Zhang ◽  
Chunxin Wang ◽  
Zhuo Zhao ◽  
Mingxin Zhang ◽  
...  

Aim The target molecule regulatory function of microRNA-21 (miR-21) in multiple signalling pathways has become a main focus of genetic and pharmacological regulatory studies of various diseases. The identification of target genes for miRNA-21 in the development of hair follicles can provide new research pathways for the regulation of cell development. Methods In the present study, eight six-month-old ewes from Super Merino (SM) and Small Tailed Han (STH) sheep breeds were selected. Target prediction and dual-luciferase wild-type and mutant vectors were used to identify the target genes of miR-21. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and bioinformatics analysis were conducted to analyze the effects of miR-21. Results The results show that the expressions of CNKSR2, KLF3 and TNPO1 were downregulated by miRNA-21 at rates of 36%, 26% and 48%, respectively. Moreover, there was a significant negative correlation between the expression of miR-21 and the three target genes in sheep with two extreme phenotypes. The expression of microRNA-21in October was significantly lower than that in January and February; while the expression of CNKSR2, KLF3 and TNPO1 in October was higher than that in January and February. Conclusions: These results suggest that CNKSR2, KLF3 and TNPO1 are three newly discovered target genes of miR-21 and might be involved in the effects of miR-21 on hair follicle development.


2020 ◽  
Author(s):  
Wei Ge ◽  
Wei-Dong Zhang ◽  
Yue-Lang Zhang ◽  
Yu-Jie Zheng ◽  
Fang Li ◽  
...  

AbstractCashmere, also known as soft gold, is produced from the secondary hair follicles in Cashmere goats and it’s therefore of significance to investigate the molecular profiles during Cashmere goat hair follicle development. However, our current understanding of the machinery underlying Cashmere goat hair follicle remains largely unexplored and researches regarding hair follicle development mainly used the mouse as a research model. To provides comprehensively understanding on the cellular heterogeneity and cell lineage cell fate decisions, we performed single-cell RNA sequencing on 19,705 single cells from induction (embryonic day 60), organogenesis (embryonic day 90) and cytodifferentiation (embryonic day 120) stages of fetus Cashmere goat dorsal skin. Unsupervised clustering analysis identified 16 cell clusters and their corresponding cell types were also unprecedentedly characterized. Based on the lineage inference, we revealed detailed molecular landscape along the dermal and epidermal cell lineage developmental pathways. Notably, by cross-species comparasion of single cell data with murine model, we revelaed conserved programs during dermal condensate fate commitment and the heterochrony development of hair follicle development between mouse and Cashmere goat were also discussed here. Our work here delineate unparalleled molecular profiles of different cell populations during Cashmere goat hair follicle morphogenesis and provide a valuable resource for identifying biomarkers during Cashmere goat hair follicle development.


2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)|>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.


2018 ◽  
Vol 29 (22) ◽  
pp. 2784-2799 ◽  
Author(s):  
Swamy K. Tripurani ◽  
Yan Wang ◽  
Ying-Xin Fan ◽  
Massod Rahimi ◽  
Lily Wong ◽  
...  

Mice that lack the epidermal growth factor receptor (EGFR) fail to develop a hair coat, but the mechanism responsible for this deficit is not completely understood. Here, we show that EGFR plays a critical role to attenuate wingless-type MMTV integration site family member (Wnt)/β-catenin signaling during postnatal hair follicle development. Genetic ablation of EGFR in mice resulted in increased mitotic activity in matrix cells, apoptosis in hair follicles, and impaired differentiation of epithelial lineages that form hair. EGFR is activated in wild-type hair follicle stem cells marked with SOX9 or NFATc1 and is essential to restrain proliferation and support stem cell numbers and their quiescence. We observed elevated levels of Wnt4, 6, 7b, 10a, 10b, and 16 transcripts and hyperactivation of the β-catenin pathway in EGFR knockout follicles. Using primary keratinocytes, we linked ligand-induced EGFR activation to suppression of nascent mRNA synthesis of Wnt genes. Overexpression of the Wnt antagonist sFRP1 in mice lacking EGFR demonstrated that elevated Wnts are a major cause for the hair follicle defects. Colocalization of transforming growth factor α and Wnts regulated by EGFR in stem cells and progeny indicates that EGFR autocrine loops control Wnts. Our findings define a novel mechanism that integrates EGFR and Wnt/β-catenin pathways to coordinate the delicate balance between proliferation and differentiation during development.


2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)|>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.


2020 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  

Abstract Background: Hair follicles is an appendage from the vertebrate skin epithelium, and arise from the embryonic ectoderm andregenerate cyclically during adult life. Dermal papilla cells (DPCs) is the key dermal component of the hair follicle that directly regulates hair follicle development, growth and regeneration. Recent studies have reported that miRNA plays an important role in regulating hair follicle morphogenesis, proliferation, differentiation and apoptosis of hair follicle stem cells. Results: The miRNAs expression profile of the DPCs from different hair density Rex rabbits shown that 240 differentially expressed of miRNAs were screened (log 2 (HD/LD)|>1.00 and Q-value≤0.001). Among them, the expression of ocu-miR-205-5p in low hair densities DPCs was higher than that in high hair densities, and it is highly expressed in the skin tissue of Rex rabbits ( P <0.05). ocu-miR-205 could increase cell proliferation and cell apoptosis ratio, change cell cycle process ( P <0.05), affect the genes expression of PI3K/Akt, Wnt, Notch and BMP signaling pathways in DPCs and skin tissue of Rex rabbits, inhibit the protein phosphorylation level of CTNNB1, GSK-3β and the protein expression level of noggin (NOG), promote Akt phosphorylation level ( P <0.05). There was no significant change in primary follicle density ( P >0.05), but the secondary follicle density and total follicle density ( P <0.05) were changed after ocu-miR-205-5p interfered expression, and secondary/primary ratio (S/P) in ocu-miR-205-5p interfered expression group increased at 14 days after injection ( P <0.05). Conclusion: ocu-miR-205 could promote the apoptosis of DPCs, affect PI3K/Akt, Wnt, Notch and BMP signaling pathways genes and proteins expression in DPCs and skin of Rex rabbits, promote the transformation of hair follicles from growth phase to regression and resting phase, and affect hair density of Rex rabbits.


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