Microenvironmental control of stem cell fate in intestinal homeostasis and disease.
Microenvironmental control of stem cell fate in intestinal homeostasis and disease.
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DOI：
10.1002/path.4563
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Leedham S
中科院分区：
文献类型：
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作者：
Biswas S;Davis H;Irshad S;Sandberg T;Worthley D;Leedham S
传统的肠上皮结构模型描述了一种单向的组织层次结构，干细胞位于隐窝底部，子代细胞在垂直(隐窝-腔)轴方向上增殖并终末分化。在这个模型中，离开了利基的细胞的命运是确定的，它的寿命是有限的。越来越多的证据表明，干细胞控制和子代细胞命运的决定不仅仅是一种固有的、细胞自主的特性，而且受到微环境的严重影响，包括旁分泌、间充质和内源性上皮形态原梯度。最近的研究表明，在肠道内稳态中，干细胞在利基内的不同能力状态之间可逆地转移。此外，破坏体内平衡的选择性压力，如肠道炎症或形态调节失调，可能会导致承诺的祖细胞，甚至一些分化的细胞重新获得干细胞特性。重要的是，最近已经表明，这种对细胞命运决定的破坏可以导致位于隐窝基础干细胞区外的细胞的体细胞突变和肿瘤性转化。本文综述了干细胞动力学在动态平衡、肠道再生和致癌方面的研究进展，并探讨了干细胞动力学对人类疾病和癌症治疗的意义。©2015作者。《病理学杂志》由John Wiley&Sons Ltd代表大不列颠和爱尔兰病理学会出版。
The conventional model of intestinal epithelial architecture describes a unidirectional tissue organizational hierarchy with stem cells situated at the crypt base and daughter cells proliferating and terminally differentiating as they progress along the vertical (crypt–luminal) axis. In this model, the fate of a cell that has left the niche is determined and its lifespan limited. Evidence is accumulating to suggest that stem cell control and daughter cell fate determination is not solely an intrinsic, cell autonomous property but is heavily influenced by the microenvironment including paracrine, mesenchymal, and endogenous epithelial morphogen gradients. Recent research suggests that in intestinal homeostasis, stem cells transit reversibly between states of variable competence in the niche. Furthermore, selective pressures that disrupt the homeostatic balance, such as intestinal inflammation or morphogen dysregulation, can cause committed progenitor cells and even some differentiated cells to regain stem cell properties. Importantly, it has been recently shown that this disruption of cell fate determination can lead to somatic mutation and neoplastic transformation of cells situated outside the crypt base stem cell niche. This paper reviews the exciting developments in the study of stem cell dynamics in homeostasis, intestinal regeneration, and carcinogenesis, and explores the implications for human disease and cancer therapies. © 2015 Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.