scholarly journals Suppression of Wnt/β-catenin signaling by EGF receptor is required for hair follicle development

2018 ◽  
Vol 29 (22) ◽  
pp. 2784-2799 ◽  
Author(s):  
Swamy K. Tripurani ◽  
Yan Wang ◽  
Ying-Xin Fan ◽  
Massod Rahimi ◽  
Lily Wong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hair Follicle ◽  
Transforming Growth Factor ◽  
Integration Site ◽  
Critical Role ◽  
Hair Follicles ◽  
Follicle Development ◽  
Genetic Ablation ◽  
Hair Follicle Development

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.

scholarly journals Chi-miR-370-3p regulates hair follicle development of Inner Mongolian cashmere goats

2021 ◽  
Author(s):  
Erhan Hai ◽  
Wenjing Han ◽  
Zhihong Wu ◽  
Rong Ma ◽  
Fangzheng Shang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Dermal Fibroblasts ◽  
Cell Counting ◽  
Follicle Development ◽  
Signalling Molecules ◽  
Cashmere Goats ◽  
Hair Follicle Development

Abstract Background MicroRNAs (miRNAs), a class of 22 nucleotide (nt) non-coding RNAs, negatively regulate mRNA post-transcriptional modification in various biological processes. Initiation of skin hair follicles in cashmere goats is a dynamic process involving many key signalling molecules, but the associated cellular biological mechanisms induced by these key signalling molecules have not been reported. Results In this study, differential expression, bioinformatics, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on miRNA expression profiles of Inner Mongolian cashmere goats at 45, 55, and 65 days during the foetal period, and chi-miR-370-3p was identified and investigated further. Real-time fluorescence quantification (qRT-PCR), dual luciferase reporting, and western blotting results showed that transforming growth factor beta receptor 2 (TGF-βR2) and fibroblast growth factor receptor 2 (FGFR2) were the target genes of chi-miR-370-3p. Chi-miR-370-3p also regulated the expression of TGF-βR2 and FGFR2 at mRNA and protein levels in epithelial cells and dermal fibroblasts. DNA staining, Cell Counting Kit-8 (CCK8), and fluorescein-labelled Annexin V results showed that chi-miR-370-3p inhibited the proliferation of epithelial cells and fibroblasts, but had no effect on apoptosis. Cell scratch test results showed that chi-miR-370-3p promoted the migration of epithelial cells and fibroblasts. Conclusion Chi-miR-370-3p inhibits the proliferation of epithelial cells and fibroblasts by targeting TGF-βR2 and FGFR2, thereby improving cell migration ability, and ultimately regulating the fate of epithelial cells and dermal fibroblasts to develop the placode (PC) and dermal condensate (DC), inducing hair follicle development.

scholarly journals Using WGCNA (weighted gene co-expression network analysis) to identify the hub genes of skin hair follicle development in fetus stage of Inner Mongolia cashmere goat

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243507
Author(s):  
Zhihong Wu ◽  
Erhan Hai ◽  
Zhengyang Di ◽  
Rong Ma ◽  
Fangzheng Shang ◽  
...  
Keyword(s):  
Network Analysis ◽  
Hair Follicle ◽  
Quantitative Polymerase Chain Reaction ◽  
Correlation Coefficients ◽  
Hair Follicles ◽  
Functional Enrichment ◽  
Follicle Development ◽  
Hub Genes ◽  
Cashmere Goats ◽  
Hair Follicle Development

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

scholarly journals Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt Pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 466 ◽  
Author(s):  
Pietro Gentile ◽  
Simone Garcovich
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Mesenchymal Stem Cell ◽  
Hair Follicle ◽  
Hair Loss ◽  
Hair Growth ◽  
Follicle Development ◽  
Hair Regrowth ◽  
Hair Follicle Development

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).

scholarly journals Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors

2020 ◽  
Vol 21 (6) ◽  
pp. 1967 ◽  
Author(s):  
Jae-Sung Ryu ◽  
Sang Young Seo ◽  
Eun-Jeong Jeong ◽  
Jong-Yeup Kim ◽  
Yong-Gon Koh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Cartilage Regeneration ◽  
Ganglioside Gm3

Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.

scholarly journals Epithelium-Mesenchyme Interactions Control the Activity of Peroxisome Proliferator-Activated Receptor β/δ during Hair Follicle Development

2005 ◽  
Vol 25 (5) ◽  
pp. 1696-1712 ◽  
Author(s):  
Nicolas Di-Poï ◽  
Chuan Young Ng ◽  
Nguan Soon Tan ◽  
Zhongzhou Yang ◽  
Brian A. Hemmings ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Follicles ◽  
Peroxisome Proliferator ◽  
Follicle Development ◽  
Paracrine Factor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Proliferation And Apoptosis ◽  
Normal Hair ◽  
Hair Follicle Development

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.

scholarly journals Melatonin Regulates the Periodic Growth of Cashmere by Upregulating the Expression of Wnt10b and β-catenin in Inner Mongolia Cashmere Goats

2021 ◽  
Vol 12 ◽  
Author(s):  
Junyang Liu ◽  
Qing Mu ◽  
Zhihong Liu ◽  
Yan Wang ◽  
Jiasen Liu ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Inner Mongolia ◽  
Growth Cycle ◽  
Hair Follicles ◽  
Skin Tissue ◽  
Follicle Development ◽  
Periodic Growth ◽  
Cashmere Goats ◽  
Hair Follicle Development ◽  
Hair Follicle Growth

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.

scholarly journals The functions of ocu-miR-205 in regulating hair follicle development of Rex rabbits

2019 ◽  
Author(s):  
Gongyan Liu ◽  
Shu Li ◽  
Hongli Liu ◽  
Yanli Zhu ◽  
Liya Bai ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Signaling Pathways ◽  
Adult Life ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Skin Tissue ◽  
Follicle Development ◽  
Hair Density ◽  
Phosphorylation Level ◽  
Hair Follicle Development

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.

scholarly journals Identification of microRNA-21 target genes associated with hair follicle development in sheep

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7167 ◽  
Author(s):  
Bo Zhai ◽  
Lichun Zhang ◽  
Chunxin Wang ◽  
Zhuo Zhao ◽  
Mingxin Zhang ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Target Genes ◽  
Target Prediction ◽  
Significant Negative Correlation ◽  
Hair Follicles ◽  
Regulatory Function ◽  
Follicle Development ◽  
Extreme Phenotypes ◽  
Hair Follicle Development ◽  
New Research

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.

scholarly journals A single-cell transcriptome atlas during Cashmere goat hair follicle morphogenesis

2020 ◽  
Author(s):  
Wei Ge ◽  
Wei-Dong Zhang ◽  
Yue-Lang Zhang ◽  
Yu-Jie Zheng ◽  
Fang Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Hair Follicle ◽  
Single Cells ◽  
Cell Lineage ◽  
Hair Follicles ◽  
Follicle Development ◽  
Cashmere Goat ◽  
Cell Fate Decisions ◽  
Molecular Profiles ◽  
Hair Follicle Development

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.

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