Differentiation of Mouse Induced Pluripotent Stem Cells into a Multipotent Keratinocyte Lineage
Differentiation of Mouse Induced Pluripotent Stem Cells into a Multipotent Keratinocyte Lineage
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DOI：
10.1038/jid.2010.364
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发表时间：
2011-04-01
影响因子：
6.5
通讯作者：
Roop, Dennis R.
中科院分区：
文献类型：
--
作者：
Bilousova, Ganna;Chen, Jiang;Roop, Dennis R.
最近在诱导多能干细胞（iPSC）生成方面取得的突破提供了一种具有胚胎干细胞样特性的新型可再生细胞来源，可潜在用于基因治疗和组织工程。尽管iPSC已分化为各种细胞类型，但尚未获得iPSC衍生的角质形成细胞。在这项研究中，我们报告了通过连续应用视黄酸和骨形态发生蛋白 4 并在 IV 型胶原包被的板上生长，小鼠 iPSC 体外分化为角质形成细胞谱系。我们证明 iPSC 可以分化为功能性角质形成细胞，能够在体内环境中再生完全分化的表皮、毛囊和皮脂腺。来自 iPSC 的角质形成细胞在基因和蛋白质表达方面表现出与原代角质形成细胞相似的特征，以及它们在体外分化和在体内测定中重建正常皮肤及其附属物的能力。目前，许多遗传性皮肤病尚无有效的治疗方法。将 iPSC 有效分化为角质形成细胞谱系的方法的开发将使我们能够确定基因校正的自体 iPSC 是否可用于为这些疾病产生永久性的纠正疗法。皮肤病学研究杂志 (2011) 131, 857-864； doi：10.1038/jid.2010.364； 2010 年 12 月 9 日在线发布
Recent breakthroughs in the generation of induced pluripotent stem cells (iPSCs) have provided a novel renewable source of cells with embryonic stem cell-like properties, which may potentially be used for gene therapy and tissue engineering. Although iPSCs have been differentiated into various cell types, iPSC-derived keratinocytes have not yet been obtained. In this study, we report the in vitro differentiation of mouse iPSCs into a keratinocyte lineage through sequential applications of retinoic acid and bone-morphogenetic protein-4 and growth on collagen IV-coated plates. We show that iPSCs can be differentiated into functional keratinocytes capable of regenerating a fully differentiated epidermis, hair follicles, and sebaceous glands in an in vivo environment. Keratinocytes derived from iPSCs displayed characteristics similar to those of primary keratinocytes with respect to gene and protein expression, as well as their ability to differentiate in vitro and to reconstitute normal skin and its appendages in an in vivo assay. At present, no effective therapeutic treatments are available for many genetic skin diseases. The development of methods for the efficient differentiation of iPSCs into a keratinocyte lineage will enable us to determine whether genetically corrected autologous iPSCs can be used to generate a permanent corrective therapy for these diseases. Journal of Investigative Dermatology (2011) 131, 857-864; doi:10.1038/jid.2010.364; published online 9 December 2010