Melatonin promotes Cashmere goat (<i>Capra hircus</i>) secondary hair follicle growth: a view from integrated analysis of long non-coding and coding RNAs

The role of melatonin in promoting the yield of Cashmere goat wool has been demonstrated for decades though there remains a lack of knowledge regarding melatonin mediated hair follicle growth. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are widely transcribed in the genome and play ubiquitous roles in regulating biological processes. However, the role of lncRNAs in regulating melatonin mediated hair follicle growth remains unclear. In this study, we established an <i>in vitro</i> Cashmere goat secondary hair follicle culture system, and demonstrated that 500 ng/L melatonin exposure promoted hair follicle fiber growth. Based on long intergenic RNA sequencing, we demonstrated that melatonin promoted hair follicle elongation via regulating genes involved in focal adhesion and extracellular matrix receptor pathways and further cis predicting of lncRNAs targeted genes indicated that melatonin mediated lncRNAs mainly targeted vascular smooth muscle contraction and signaling pathways regulating the pluripotency of stem cells. We proposed that melatonin exposure not only perturbed key signals secreted from hair follicle stem cells to regulate hair follicle development, but also mediated lncRNAs mainly targeted to pathways involved in the microvascular system and extracellular matrix, which constitute the highly orchestrated microenvironment for hair follicle stem cell. Taken together, our findings here provide a profound view of lncRNAs in regulating Cashmere goat hair follicle circadian rhythms and broaden our knowledge on melatonin mediated hair follicle morphological changes.数十年来，褪黑素（melatonin）提升绒山羊（Cashmere goat）羊绒产量的作用已得到广泛证实，但学界对褪黑素介导的毛囊生长机制仍缺乏系统认知。现有研究表明，长链非编码RNA（long non-coding RNAs, lncRNAs）在基因组中广泛转录，且在各类生物学过程的调控中发挥着不可或缺的作用。然而，长链非编码RNA在调控褪黑素介导的毛囊生长过程中所扮演的角色仍未明确。本研究构建了绒山羊次级毛囊体外（in vitro）培养体系，证实500 ng/L浓度的褪黑素暴露可促进毛囊纤维生长。基于基因间长链RNA测序结果，本研究发现褪黑素可通过调控黏着斑与细胞外基质受体通路相关基因，促进毛囊伸长；进一步对长链非编码RNA靶基因开展顺式预测分析显示，褪黑素介导的长链非编码RNA主要靶向血管平滑肌收缩及干细胞多能性调控信号通路。本研究提出，褪黑素暴露不仅干扰了毛囊干细胞分泌的调控毛囊发育的关键信号，还通过调控长链非编码RNA靶向微血管系统与细胞外基质相关通路——而后者正是构建毛囊干细胞高度协调微环境的核心组分。综上，本研究结果为阐明长链非编码RNA调控绒山羊毛囊节律提供了深刻视角，也拓展了学界对褪黑素介导的毛囊形态变化的认知。