Niche support of human intestinal stem cells

摘要 肠道发育是一个高度复杂的过程，涉及肠道之间的相互信号。 上皮和底层间充质，以推动形态发生过程，从而产生 成人全功能肠道的典型隐窝-绒毛结构。然而，几乎什么都不知道。 关于人类肠道中存在的构成肠道干细胞(ISC)生态位的细胞成分， 对于这些细胞如何在功能上调节人类ISCs，更是知之甚少。改善这一差距 在知识上是至关重要的，对于我们了解正常的人体肠道，也会打下基础 了解疾病的分子和细胞基础，并开发旨在 刺激修复和再生。这项提议的目标是增加人类基本的新知识 肠道生物学，通过询问从发育到生命周期的ISC生态位 成年期，并了解利基细胞如何支持人类ISCs、肠道成熟和 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.