Identification of dermal papilla derived agents which transform the terminalhair to vellus hair

(1)从患有雄激素性脱发的男性受试者的秃顶病变和非秃顶枕病变中切除的毛囊中培养出两种类型的真皮乳头细胞。然后从这两种类型的真皮乳头细胞（DPCs）中提取总rna，并以低聚dt尾pUC19为引物构建3'导向cDNA文库。两个文库各随机抽取约1000个菌落，测定每个cDNA的核苷酸序列，并将基因表达谱与数据库（BodyMap）进行比较。我们将他们分为三组；1)新基因在正常对照DPCs中高表达，而在秃发DPCs中不表达。2)新基因在秃发DPCs中高表达，而在正常对照DPCs中不表达。3)两者之间表达差异很大的已知基因。I型胶原蛋白，纤维连接蛋白和骨连接蛋白，在两个文库中克隆了10次或更多，这意味着DPCs大量产生这些细胞外基质。在硅胶对比中，所鉴定的控制dpc特异性基因和秃dpc特异性基因都在真皮乳头细胞中特异性表达。最后，我们选择了8个候选基因，并通过开发这些基因的敲除动物来研究它们的表达谱和功能。检测毛囊中甲状腺激素受体的表达。组成毛囊的所有细胞均为T3受体阳性。此外，在生理浓度下，T3对培养毛囊细胞的生长活性最高(3)。获得抗人真皮乳头单克隆抗体。其中一个被证实识别出一种新的角蛋白。

(1). Two types of dermal papilla cells were cultured from the excised hair follicles obtained from the bald lesion and non bald occipital lesion of a male subject afflicted with an androgenic alopecia. Then total RNAs were extracted from those two tupes of dermal papilla cells (DPCs), and 3'-directed cDNA libraly were constructed using oligo-dT tailed pUC19 as a primer. Approximately 1000 each colonies were picked up randomly for both libraries, and nucleotide sequence of each cDNA was determined, and gene expression profiles were compared with the data base (BodyMap) ose. The we categorize them into 3 groups ; 1) new genes highly expressed in normal control DPCs but not in the bald DPCs. 2) new genes highly expressed in the bald DPCs but not in normal control DPCs. 3) known genes whose expression is highly different between the two. Type I collagen, fibronectin, and osteonectin, which were cloned ten times or more in both libraries, which means that DPCs abundantly produce those extracellular matrix. In sillicob comparison of the genes identified control DPC-specific and bald DPC-specific genes, all of which were speciffically expressed in dermal papilla cells. Finally we chose 8 candidate genes and whose expression profiles and functions are now being studied by means of developing knock-out animals of those genes.(2). Thyroid hormone receptor expression was examined in the hair folicle. All cells which compose the hair follicle were T3 receptor positive. In addition, the activity of T3 on the growth of cultured hair follicle cells is highest at the phisiological concentration.(3). Monoclonal antibodies against human dermal papilla were obtained. One of which was confirmed to recognize a new keratin.