Kearns Nicola A, Genga Ryan M J, Ziller Michael, Kapinas Kristina, Peters Heiko, Brehm Michael A, Meissner Alexander, Maehr René
Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
Stem Cell Res. 2013 Nov;11(3):1003-12. doi: 10.1016/j.scr.2013.06.007. Epub 2013 Jun 29.
Anterior foregut endoderm (AFE) gives rise to therapeutically relevant cell types in tissues such as the esophagus, salivary glands, lung, thymus, parathyroid and thyroid. Despite its importance, reports describing the generation of AFE from pluripotent stem cells (PSCs) by directed differentiation have mainly focused on the Nkx2.1(+) lung and thyroid lineages. Here, we describe a novel protocol to derive a subdomain of AFE, identified by expression of Pax9, from PSCs using small molecules and defined media conditions. We generated a reporter PSC line for isolation and characterization of Pax9(+) AFE cells, which when transplanted in vivo, can form several distinct complex AFE-derived epithelia, including mucosal glands and stratified squamous epithelium. Finally, we show that the directed differentiation protocol can be used to generate AFE from human PSCs. Thus, this work both broadens the range of PSC-derived AFE tissues and creates a platform enabling the study of AFE disorders.
前肠内胚层（AFE）可分化为食管、唾液腺、肺、胸腺、甲状旁腺和甲状腺等组织中具有治疗意义的细胞类型。尽管其很重要，但关于通过定向分化从多能干细胞（PSC）生成AFE的报道主要集中在Nkx2.1（+）肺和甲状腺谱系。在此，我们描述了一种新方案，利用小分子和特定培养基条件从PSC中衍生出由Pax9表达所鉴定的AFE亚结构域。我们构建了一个报告PSC系，用于分离和鉴定Pax9（+）AFE细胞，这些细胞在体内移植时可形成几种不同的复杂AFE来源上皮，包括粘膜腺和复层鳞状上皮。最后，我们证明该定向分化方案可用于从人PSC生成AFE。因此，这项工作既拓宽了PSC衍生的AFE组织范围，又创建了一个能够研究AFE疾病的平台。
