Jiang Yao, Liu Huatao, Zou Quan, Li Shujuan, Ding Xiangdong
National Engineering Laboratory for Animal Breeding, Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.
Anhui Provincial Key Laboratory of Livestock and Poultry Product Safety Engineering, Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, Hefei, China.
Front Cell Dev Biol. 2022 May 12;10:902026. doi: 10.3389/fcell.2022.902026. eCollection 2022.
Hair placode formation is an important stage of hair follicle morphogenesis and it is a complex process facilitated by non-coding RNAs. In this study, we conducted whole transcriptome sequencing analysis of skin, heart, liver, lung, and kidney tissues of day 41 (E41) normal and hairless pig embryos, and respectively detected 15, 8, and 515 skin-specific differentially expressed (DE) lncRNAs, miRNAs, and mRNAs. Furthermore, 18 competing endogenous RNA (ceRNA) networks were constructed. Following weighted gene co-expression network analysis (WGCNA) of stages E39, E41, E45, E52, and E60, between normal and hairless pig embryos, only two ceRNAs (lncRNA2162.1/miR-29a-5p/BMPR1b and lncRNA627.1/miR-29a-5p/EDAR) that showed period-specific differential expression in E41 skin were retained. Dual-luciferase reporter assays further indicated that was a direct, functioning target of and that no binding site was found in BMPR1b. Moreover, overexpression inhibited the mRNA and protein expression of while no significant differential expression of BMPR1b was detected. In addition, over-expressed lncRNA627.1 reduces the expression of and increase EDAR expression while inhibits lncRNA627.1 resulted in a opposite expression trend. Cell proliferation result demonstrated that lower expression of EDAR and lncRNA627.1 inhibited hair placode precursor cells (HPPCs) proliferation in a manner similar to that shown by over-expressed . This study identified that inhibited HPPCs proliferation the suppression of expression in the EDA/EDAR signaling pathway, while lncRNA627.1 rescues EDAR expression. Our study provides a basis for a better understanding of the mechanisms underlying the ceRNA complex, miR29a-5p/EDAlncRNA627.1, that could regulate hair placode formation, which may help decipher diseases affecting human hair.
毛基板形成是毛囊形态发生的一个重要阶段，并且是一个由非编码RNA促进的复杂过程。在本研究中，我们对41日龄（E41）正常和无毛猪胚胎的皮肤、心脏、肝脏、肺和肾脏组织进行了全转录组测序分析，分别检测到15、8和515个皮肤特异性差异表达（DE）的长链非编码RNA（lncRNA）、微小RNA（miRNA）和信使RNA（mRNA）。此外，构建了18个竞争性内源RNA（ceRNA）网络。在对正常和无毛猪胚胎的E39、E41、E45、E52和E60阶段进行加权基因共表达网络分析（WGCNA）后，仅保留了两个在E41皮肤中表现出阶段特异性差异表达的ceRNA（lncRNA2162.1/miR - 29a - 5p/BMPR1b和lncRNA627.1/miR - 29a - 5p/EDAR）。双荧光素酶报告基因检测进一步表明，[此处原文缺失部分内容]是[此处原文缺失部分内容]的直接作用靶点，且在BMPR1b中未发现结合位点。此外，[此处原文缺失部分内容]过表达抑制了[此处原文缺失部分内容]的mRNA和蛋白表达，而未检测到BMPR1b有显著差异表达。另外，过表达的lncRNA627.1降低了[此处原文缺失部分内容]的表达并增加了EDAR的表达，而抑制lncRNA627.1则导致相反的表达趋势。细胞增殖结果表明，EDAR和lncRNA627.1的低表达以类似于[此处原文缺失部分内容]过表达所显示的方式抑制了毛基板前体细胞（HPPCs）的增殖。本研究确定，[此处原文缺失部分内容]通过抑制EDA/EDAR信号通路中[此处原文缺失部分内容]的表达来抑制HPPCs增殖，而lncRNA627.1可挽救EDAR的表达。我们的研究为更好地理解ceRNA复合物miR29a - 5p/EDAlncRNA627.1调控毛基板形成的机制提供了基础，这可能有助于解读影响人类毛发的疾病。
