Human Fetal Scalp Dermal Papilla Enriched Genes and the Role of R-Spondin-1 in the Restoration of Hair Neogenesis in Adult Mouse Cells.
Human Fetal Scalp Dermal Papilla Enriched Genes and the Role of R-Spondin-1 in the Restoration of Hair Neogenesis in Adult Mouse Cells.
复制标题
DOI：
10.3389/fcell.2020.583434
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Chuong CM
中科院分区：
文献类型：
--
作者：
Weber EL;Lai YC;Lei M;Jiang TX;Chuong CM
关于控制真皮乳头 (DP) 诱导毛囊新生能力的调节网络仍有很多未知之处，这种能力随着年龄的增长而大大降低。为了进一步定义表征 DP 细胞的核心基因，并确定具有更大毛发诱导能力的 DP 细胞中突出的通路，对人类胎儿和成人真皮毛囊细胞进行了比较转录组分析。与胎儿真皮鞘杯 (DSC) 细胞和滤泡间真皮 (IFD) 群体相比，胎儿 DP 细胞中有 121 个基因显着上调。将富集的人类胎儿 DP 基因组与人类成年 DP、新生小鼠 DP 和胚胎小鼠真皮浓缩 (DC) 细胞进行比较，揭示了 Wnt/β-连环蛋白、Shh、FGF、BMP 和 Notch 信号通路表达的差异。我们选择 R-spondin-1（一种 Wnt 激动剂）进行功能验证，并在皮肤重建测定中表明，外源给药可恢复成年小鼠细胞的毛囊新生。为了探索胎儿 DP 基因表达的上游调节因子，我们鉴定了 29 个转录因子，与成人 DP 细胞相比，这些转录因子在人胎儿 DP 细胞中表达上调。其中，七个转录因子结合基序在胎儿和成人 DP 细胞之间差异表达的基因的候选启动子区域中显着富集，表明在赋予胎儿 DP 表型的调节网络中具有潜在作用，并且可能与诱导卵泡新生有关。
Much remains unknown about the regulatory networks which govern the dermal papilla’s (DP) ability to induce hair follicle neogenesis, a capacity which decreases greatly with age. To further define the core genes which characterize the DP cell and to identify pathways prominent in DP cells with greater hair inductive capacity, comparative transcriptome analyses of human fetal and adult dermal follicular cells were performed. 121 genes were significantly upregulated in fetal DP cells in comparison to both fetal dermal sheath cup (DSC) cells and interfollicular dermal (IFD) populations. Comparison of the set of enriched human fetal DP genes with human adult DP, newborn mouse DP, and embryonic mouse dermal condensation (DC) cells revealed differences in the expression of Wnt/β-catenin, Shh, FGF, BMP, and Notch signaling pathways. We chose R-spondin-1, a Wnt agonist, for functional verification and show that exogenous administration restores hair follicle neogenesis from adult mouse cells in skin reconstitution assays. To explore upstream regulators of fetal DP gene expression, we identified twenty-nine transcription factors which are upregulated in human fetal DP cells compared to adult DP cells. Of these, seven transcription factor binding motifs were significantly enriched in the candidate promoter regions of genes differentially expressed between fetal and adult DP cells, suggesting a potential role in the regulatory network which confers the fetal DP phenotype and a possible relationship to the induction of follicle neogenesis.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
21.1
作者：
Davenport AP;Hyndman KA;Dhaun N;Southan C;Kohan DE;Pollock JS;Pollock DM;Webb DJ;Maguire JJ
通讯作者：
Maguire JJ
影响因子：
2.7
作者：
Chiang, C;Swan, RZ;Dlugosz, AA
通讯作者：
Dlugosz, AA
DOI：
10.1073/pnas.1309970110
发表时间：
2013-12-03
影响因子：
11.1
作者：
Higgins, Claire A.;Chen, James C.;Christiano, Angela M.
通讯作者：
Christiano, Angela M.
影响因子：
6
作者：
Botchkareva, NV;Botchkarev, VA;Paus, R
通讯作者：
Paus, R