Generating human hair follicle cell lines and 3-D histiotypic models of the human hair follicle using human induced pluripotent stem cells

战略性研究重点：世界一流的生物科学头发相关疾病不会危及生命；然而，由于脱发的美学和社会对头发的看法，它们会给个体患者带来心理困扰。脱发可能涉及两种生理病理；每天头发脱落增多（脱发）或无毛（脱发）。遗传或环境因素可以引发男性和女性的头发疾病。头发疾病有许多不同的类别；最常见的是雄激素性脱发（AGA），影响多达70%的男性和40%的女性。虽然目前一些类型的脱发疾病有现成和有效的治疗方法；对某些亚型疾病的治疗极为有限。毛囊生物工程与分子生物学相结合，可以更好地探索未来的治疗方法，并进一步加深对毛囊生物学的了解。最近细胞生物学的一个重要里程碑是诱导多能干细胞（iPSCs）的发展。2006年，Yamanaka报道，可以从小鼠体细胞中产生具有与胚胎干细胞（ECSs）相似特征的细胞。这是通过过度表达四个关键因素实现的；OCT4, SOX2， KLF4和MYC，现在被称为“山中因子”。自诞生以来，iPSC技术因其在干细胞生物学和再生医学领域的前景而迅速发展。重要的是，iPSC技术也在疾病建模中得到了应用，开创了“培养皿中的疾病”模型，该模型已被用于对疾病机制的基本理解，以及药物发现和筛选。在这个项目中，我们的目标是利用人类多能干细胞开发一个强大的分化方案，以产生毛囊谱系细胞。此外，我们的目标是使用生成的细胞系来产生毛囊的2D和3D模型，以更好地研究健康和疾病的头发生物学。

Strategic Research Priority: World Class BioscienceHair related disorders are not life threatening; however, they can cause psychological distress to individual sufferers due to the aesthetics of hair loss and societal perceptions of hair. Hair loss may refer to two physiopathologies; increased daily hair shedding (effluvium) or hairlessness (alopecia). Genetic or environmental factors can instigate hair disorders in both males and females. There are many different categories of hair disorder; the most common being androgenetic alopecia (AGA) affecting up to 70% of males, and 40% of females. While currently some types of hair loss disorders have readily available and efficacious therapies; the treatment for some subtypes of disorder are extremely limited. Bioengineering of the hair follicle, coupled with molecular biology could be used to better explore future therapeutic approaches and further the current understanding of hair follicle biology.A recent major milestone of cell biology was the development of induced pluripotent stem cells (iPSCs). In 2006, Yamanaka reported that cells with a similar profile to embryonic stem cells (ECSs) could be produced from murine somatic cells. This was achieved through overexpression of four key factors; OCT4, SOX2, KLF4 and MYC, now termed the 'Yamanaka factors'. Since its origin, iPSC technology has rapidly developed due to the promise it shows in the fields of stem cell biology and regenerative medicine. Importantly, there is also an application of iPSC technology in disease modelling, ushering in the advent of 'disease in a dish' models which have been used for basic understanding of disease mechanisms, as well as for drug discovery and screening. In this project, we aim to use human iPSCs to develop a robust differentiation protocol to generate hair follicle lineage cells. Additionally, we aim to use generated cell lineages to produce 2D and 3D models of the hair follicle to better investigate hair biology in both health and disease.