Dataset Information

Analysis of the sheep trichohyalin gene: potential structural and calcium-binding roles of trichohyalin in the hair follicle.

ABSTRACT: Trichohyalin is a structural protein that is produced and retained in the cells of the inner root sheath and medulla of the hair follicle. The gene for sheep trichohyalin has been purified and the complete amino acid sequence of trichohyalin determined in an attempt to increase the understanding of the structure and function of this protein in the filamentous network of the hardened inner root sheath cells. Sheep trichohyalin has a molecular weight of 201,172 and is characterized by the presence of a high proportion of glutamate, arginine, glutamine, and leucine residues, together totaling more than 75% of the amino acids. Over 65% of trichohyalin consists of two sets of tandem peptide repeats which are based on two different consensus sequences. Trichohyalin is predicted to form an elongated alpha-helical rod structure but does not contain the sequences required for the formation of intermediate filaments. The amino terminus of trichohyalin contains two EF hand calcium-binding domains indicating that trichohyalin plays more than a structural role within the hair follicle. In situ hybridization studies have shown that trichohyalin is expressed in the epithelia of the tongue, hoof, and rumen as well as in the inner root sheath and medulla of the hair follicle.

SUBMITTER: Fietz MJ

PROVIDER: S-EPMC2119783 | biostudies-other | 1993 May

REPOSITORIES: biostudies-other

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Analysis of the sheep trichohyalin gene: potential structural and calcium-binding roles of trichohyalin in the hair follicle.

Fietz M J MJ McLaughlan C J CJ Campbell M T MT Rogers G E GE

The Journal of cell biology 19930501 4

Trichohyalin is a structural protein that is produced and retained in the cells of the inner root sheath and medulla of the hair follicle. The gene for sheep trichohyalin has been purified and the complete amino acid sequence of trichohyalin determined in an attempt to increase the understanding of the structure and function of this protein in the filamentous network of the hardened inner root sheath cells. Sheep trichohyalin has a molecular weight of 201,172 and is characterized by the presence ...[more]

PMID: 7684041

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Project description:BackgroundMerino sheep exhibit high wool production and excellent wool quality. The fleece of Merino sheep is predominantly composed of wool fibers grown from hair follicles (HFs). The HF is a complex biological system involved in a dynamic process governed by gene regulation, and gene expression is regulated by microRNAs (miRNAs). miRNA inhibits posttranscriptional gene expression by specifically binding to target messenger RNA (mRNA) and plays an important role in regulating gene expression, the cell cycle and biological development sequences. The purpose of this study was to examine mRNA and miRNA binding to identify key miRNAs and target genes related to HF development. This will provide new and important insights into fundamental mechanisms that regulate cellular activity and cell fate decisions within and outside of the skin.ResultsWe analyzed miRNA data in skin tissues collected from 18 Merino sheep on four embryonic days (E65, E85, E105 and E135) and two postnatal days (D7 and D30) and identified 87 differentially expressed miRNAs (DE-miRNAs). These six stages were further divided into two longer developmental stages based on heatmap cluster analysis, and the results showed that DE-mRNAs in Stage A were closely related to HF morphogenesis. A coanalysis of Stage A DE-mRNAs and DE-miRNAs revealed that 9 DE-miRNAs and 17 DE-mRNAs presented targeting relationships in Stage A. We found that miR-23b and miR-133 could target and regulate ACVR1B and WNT10A. In dermal fibroblasts, the overexpression of miR-133 significantly reduced the mRNA and protein expression levels of ACVR1B. The overexpression of miR-23b significantly reduced the mRNA and protein expression levels of WNT10A.ConclusionThis study provides a new reference for understanding the molecular basis of HF development and lays a foundation for further improving sheep HF breeding. miRNAs and target genes related to hair follicular development were found, which provided a theoretical basis for molecular breeding for the culture of fine-wool sheep.

Project description:BackgroundMerino sheep are the most famous fine wool sheep in the world. They have high wool production and excellent wool quality and have attracted worldwide attention. The fleece of the Merino sheep is composed predominantly of wool fibers grown from secondary wool follicles. Therefore, it is necessary to study the development of hair follicles to understand the mechanism of wool production. The hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. The hair follicle development process is very complex and poorly understood. The purpose of our research is to identify candidate genes related to hair follicle development, provide a theoretical molecular breeding basis for the cultivation of fine wool sheep, and provide a reference for the problems of hair loss and alopecia areata that affect human beings.ResultsWe analyzed mRNAs data in skin tissues of 18 Merino sheep at four embryonic days (E65, E85, E105 and E135) and two postnatal days (P7 and P30). G1 to G6 represent hair follicles developmental at six stages (i.e. E65 to P30). We identified 7879 differentially expressed genes (DEGs) and 12623 novel DEGs, revealed different expression patterns of these DEGs at six stages of hair follicle development, and demonstrated their complex interactions. DEGs with stage-specific expression were significantly enriched in epidermal differentiation and development, hair follicle development and hair follicle morphogenesis and were enriched in many pathways related to hair follicle development. The key genes (LAMA5, WNT10A, KRT25, SOSTDC1, ZDHHC21, FZD1, BMP7, LRP4, TGFβ2, TMEM79, SOX10, ITGB4, KRT14, ITGA6, and GLI2) affecting hair follicle morphogenesis were identified by network analysis.ConclusionThis study provides a new reference for the molecular basis of hair follicle development and lays a foundation for further improving sheep hair follicle breeding. Candidate genes related to hair follicular development were found, which provided a theoretical basis for molecular breeding for the culture of fine wool sheep. These results are a valuable resource for biological investigations of fleece evolution in animals.

Project description:Wool is the critical textile raw material which is produced by the hair follicle of sheep. Therefore, it has important implications to investigate the molecular mechanism governing hair follicle development. Due to high cellular heterogeneity as well as the insufficient cellular, molecular, and spatial characterization of hair follicles on sheep, the molecular mechanisms involved in hair follicle development and wool curvature of sheep remains largely unknown. Single-cell RNA sequencing (scRNA-seq) technologies have made it possible to comprehensively dissect the cellular composition of complex skin tissues and unveil the differentiation and spatial signatures of epidermal and hair follicle development. However, such studies are lacking so far in sheep. Here, single-cell suspensions from the curly wool and straight wool lambskins were prepared for unbiased scRNA-seq. Based on UAMP dimension reduction analysis, we identified 19 distinct cell populations from 15,830 single-cell transcriptomes and characterized their cellular identity according to specific gene expression profiles. Furthermore, novel marker gene was applied in identifying dermal papilla cells isolated in vitro. By using pseudotime ordering analysis, we constructed the matrix cell lineage differentiation trajectory and revealed the dynamic gene expression profiles of matrix progenitors' commitment to the hair shaft and inner root sheath (IRS) cells. Meanwhile, intercellular communication between mesenchymal and epithelial cells was inferred based on CellChat and the prior knowledge of ligand-receptor pairs. As a result, strong intercellular communication and associated signaling pathways were revealed. Besides, to clarify the molecular mechanism of wool curvature, differentially expressed genes in specific cells between straight wool and curly wool were identified and analyzed. Our findings here provided an unbiased and systematic view of the molecular anatomy of sheep hair follicle comprising 19 clusters; revealed the differentiation, spatial signatures, and intercellular communication underlying sheep hair follicle development; and at the same time revealed the potential molecular mechanism of wool curvature, which will give important new insights into the biology of the sheep hair follicle and has implications for sheep breeding.

Project description:BackgroundCharacterization of the molecular mechanisms underlying hair follicle development is of paramount importance in the genetic improvement of wool-related traits in sheep and skin-related traits in humans. The Merino is the most important breed of fine-wooled sheep in the world. In this study, we systematically investigated the complexity of sheep hair follicle development by integrating transcriptome and methylome datasets from Merino sheep skin.ResultsWe analysed 72 sequence datasets, including DNA methylome and the whole transcriptome of four gene types, i.e. protein-coding genes (PCGs), lncRNAs, circRNAs, and miRNAs, across four embryonic days (E65, E85, E105, and E135) and two postnatal days (P7 and P30) from the skin tissue of 18 Merino sheep. We revealed distinct expression profiles of these four gene types across six hair follicle developmental stages, and demonstrated their complex interactions with DNA methylation. PCGs with stage-specific expression or regulated by stage-specific lncRNAs, circRNAs, and miRNAs were significantly enriched in epithelial differentiation and hair follicle morphogenesis. Regulatory network and gene co-expression analyses identified key transcripts controlling hair follicle development. We further predicted transcriptional factors (e.g. KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3) with stage-specific involvement in hair follicle morphogenesis. Through integrating these stage-specific genomic features with results from genome-wide association studies (GWAS) of five wool-related traits in 7135 Merino sheep, we detected developmental stages and genes that were relevant with wool-related traits in sheep. For instance, genes that were specifically upregulated at E105 were significantly associated with most of wool-related traits. A phenome-wide association study (PheWAS) demonstrated that candidate genes of wool-related traits (e.g. SPHK1, GHR, PPP1R27, CSRP2, EEF1A2, and PTPN1) in sheep were also significantly associated with dermatological, metabolic, and immune traits in humans.ConclusionsOur study provides novel insights into the molecular basis of hair follicle morphogenesis and will serve as a foundation to improve breeding for wool traits in sheep. It also indicates the importance of studying gene expression in the normal development of organs in understanding the genetic architecture of economically important traits in livestock. The datasets generated here are useful resources for functionally annotating the sheep genome, and for elucidating early skin development in mammals, including humans.

Dataset Information

Analysis of the sheep trichohyalin gene: potential structural and calcium-binding roles of trichohyalin in the hair follicle.

Publications

Analysis of the sheep trichohyalin gene: potential structural and calcium-binding roles of trichohyalin in the hair follicle.

Similar Datasets

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