Niche support of human intestinal stem cells

摘要 肠道发育是一个高度复杂的过程，涉及肠道细胞之间的相互信号传导。 上皮细胞和下面的间充质，以驱动形态发生过程，产生 完整功能的成年肠道的典型隐窝-绒毛结构。然而，几乎一无所知 关于存在于人类肠道中的构成肠道干细胞（ISC）小生境的细胞成分， 更不了解这些细胞如何在功能上调节人类ISCs。改善这一差距 对于我们理解正常的人类肠道至关重要， 了解疾病的分子和细胞基础，并开发新的治疗方法， 刺激修复和再生。这项提案的目的是增加人类的基本新知识， 肠道生物学通过询问整个人类寿命的ISC生态位，从发育到 成年期，并了解生态位细胞如何发挥作用，以支持人类ISCs，肠道成熟， 肠道功能

ABSTRACT Intestine development is a highly complex process that involves reciprocal signaling between the intestinal epithelium and the underlying mesenchyme in order to drive the morphogenetic process giving rise to the stereotypical crypt-villus architecture of the fully functional, adult intestine. However, almost nothing is known about the cellular constituents present in the human intestine that comprise the intestinal stem cell (ISC) niche, and even less is understood about how these cells may functionally regulate human ISCs. Improving this gap in knowledge is critical for our understanding of the normal human intestine, and will also lay the groundwork for understanding the molecular and cellular basis of disease and for developing novel therapies aimed at stimulating repair and regeneration. The goal of this proposal is to add fundamental new knowledge of human intestinal biology by interrogating the ISC niche across the human lifespan, from development through adulthood, and to understand how niche cells function to support human ISCs, intestinal maturation and intestinal function.