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      Integrative analysis reveals ncRNA-mediated molecular regulatory network driving secondary hair follicle regression in cashmere goats

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          Abstract

          Background

          Cashmere is a keratinized product derived from the secondary hair follicles (SHFs) of cashmere goat skins. The cashmere fiber stops growing following the transition from the actively proliferating anagen stage to the apoptosis-driven catagen stage. However, little is known regarding the molecular mechanisms responsible for the occurrence of apoptosis in SHFs, especially as pertains to the role of non-coding RNAs (ncRNAs) and their interactions with other molecules. Hair follicle (HF) degeneration is caused by localized apoptosis in the skin, while anti-apoptosis pathways may coexist in adjacent HFs. Thus, elucidating the molecular interactions responsible for apoptosis and anti-apoptosis in the skin will provide insights into HF regression.

          Results

          We used multiple-omics approaches to systematically identify long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs expressed in cashmere goat skins in two crucial phases (catagen vs. anagen) of HF growth. Skin samples were collected from three cashmere goats at the anagen (September) and catagen (February) stages, and six lncRNA libraries and six miRNA libraries were constructed for further analysis. We identified 1122 known and 403 novel lncRNAs in the goat skins, 173 of which were differentially expressed between the anagen and catagen stages. We further identified 3500 gene-encoding transcripts that were differentially expressed between these two phases. We also identified 411 known miRNAs and 307 novel miRNAs, including 72 differentially expressed miRNAs. We further investigated the target genes of lncRNAs via both cis- and trans-regulation during HF growth. Our data suggest that lncRNAs and miRNAs act synergistically in the HF growth transition, and the catagen inducer factors (TGFβ1 and BDNF) were regulated by miR-873 and lnc108635596 in the lncRNA-miRNA-mRNA networks.

          Conclusion

          This study enriches the repertoire of ncRNAs in goats and other mammals, and contributes to a better understanding of the molecular mechanisms of ncRNAs involved in the regulation of HF growth and regression in goats and other hair-producing species.

          Electronic supplementary material

          The online version of this article (10.1186/s12864-018-4603-3) contains supplementary material, which is available to authorized users.

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          Most cited references38

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          The hair follicle as a dynamic miniorgan.

          Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social interactions. The hair shaft consists of terminally differentiated keratinocytes that are produced by the hair follicle. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal-mesodermal interactions. After birth, mature and actively growing hair follicles eventually become anchored in the subcutis, and periodically regenerate by spontaneously undergoing repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and relative quiescence (telogen). Our molecular understanding of hair follicle biology relies heavily on mouse mutants with abnormalities in hair structure, growth, and/or pigmentation. These mice have allowed novel insights into important general molecular and cellular processes beyond skin and hair biology, ranging from organ induction, morphogenesis and regeneration, to pigment and stem cell biology, cell proliferation, migration and apoptosis. In this review, we present basic concepts of hair follicle biology and summarize important recent advances in the field.
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            Control of hair growth and follicle size by VEGF-mediated angiogenesis.

            The murine hair follicle undergoes pronounced cyclic expansion and regression, leading to rapidly changing demands for its vascular support. Our study aimed to quantify the cyclic changes of perifollicular vascularization and to characterize the biological role of VEGF for hair growth, angiogenesis, and follicle cycling. We found a significant increase in perifollicular vascularization during the growth phase (anagen) of the hair cycle, followed by regression of angiogenic blood vessels during the involution (catagen) and the resting (telogen) phase. Perifollicular angiogenesis was temporally and spatially correlated with upregulation of VEGF mRNA expression by follicular keratinocytes of the outer root sheath, but not by dermal papilla cells. Transgenic overexpression of VEGF in outer root sheath keratinocytes of hair follicles strongly induced perifollicular vascularization, resulting in accelerated hair regrowth after depilation and in increased size of hair follicles and hair shafts. Conversely, systemic treatment with a neutralizing anti-VEGF antibody led to hair growth retardation and reduced hair follicle size. No effects of VEGF treatment or VEGF blockade were observed in mouse vibrissa organ cultures, which lack a functional vascular system. These results identify VEGF as a major mediator of hair follicle growth and cycling and provide the first direct evidence that improved follicle vascularization promotes hair growth and increases hair follicle and hair size.
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              Controls of hair follicle cycling.

              K Stenn, R Paus (2001)
              Nearly 50 years ago, Chase published a review of hair cycling in which he detailed hair growth in the mouse and integrated hair biology with the biology of his day. In this review we have used Chase as our model and tried to put the adult hair follicle growth cycle in perspective. We have tried to sketch the adult hair follicle cycle, as we know it today and what needs to be known. Above all, we hope that this work will serve as an introduction to basic biologists who are looking for a defined biological system that illustrates many of the challenges of modern biology: cell differentiation, epithelial-mesenchymal interactions, stem cell biology, pattern formation, apoptosis, cell and organ growth cycles, and pigmentation. The most important theme in studying the cycling hair follicle is that the follicle is a regenerating system. By traversing the phases of the cycle (growth, regression, resting, shedding, then growth again), the follicle demonstrates the unusual ability to completely regenerate itself. The basis for this regeneration rests in the unique follicular epithelial and mesenchymal components and their interactions. Recently, some of the molecular signals making up these interactions have been defined. They involve gene families also found in other regenerating systems such as fibroblast growth factor, transforming growth factor-beta, Wnt pathway, Sonic hedgehog, neurotrophins, and homeobox. For the immediate future, our challenge is to define the molecular basis for hair follicle growth control, to regenerate a mature hair follicle in vitro from defined populations, and to offer real solutions to our patients' problems.
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                Author and article information

                Contributors
                royouzhouguang@126.com
                kangdanju@126.com
                372868378@qq.com
                992086702@qq.com
                117655297@qq.com
                yangyuxin2002@126.com
                xiaolongwang@nwafu.edu.cn
                +86 29 8709 1130 , chenyulin@nwafu.edu.cn
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                27 March 2018
                27 March 2018
                2018
                : 19
                : 222
                Affiliations
                ISNI 0000 0004 1760 4150, GRID grid.144022.1, College of Animal Science and Technology, , Northwest A&F University, ; Yangling, 712100 China
                Author information
                http://orcid.org/0000-0003-1620-1344
                Article
                4603
                10.1186/s12864-018-4603-3
                5870523
                29291715
                782aa650-3925-424b-9800-088bd28215e0
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 December 2017
                : 13 March 2018
                Funding
                Funded by: National Natural Science Foundation of China (CN)
                Award ID: 31372279
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31572369
                Award ID: 31772571
                Award ID: 31402038
                Award Recipient :
                Funded by: China Agriculture Research System
                Award ID: CARS-39
                Award Recipient :
                Funded by: Key Research Program of Shaanxi Province
                Award ID: 2017NY-072
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Genetics
                hair follicle,lncrna,mirna,skin,capra hircus
                Genetics
                hair follicle, lncrna, mirna, skin, capra hircus

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