Feedback regulation in multistage cell lineages.
Feedback regulation in multistage cell lineages.
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DOI：
10.3934/mbe.2009.6.59
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Nie Q
中科院分区：
文献类型：
--
作者：
Lo WC;Chou CS;Gokoffski KK;Wan FY;Lander AD;Calof AL;Nie Q
对发育和自我更新组织的研究表明，分化的细胞类型通常是通过多阶段细胞系的作用来指定的。这种谱系通常包括干细胞和多祖细胞（转运扩增；TA）阶段，最终产生终分化（TD）细胞。在一些情况下，干细胞和祖细胞在这些谱系中的自我更新和分化已被证明是在反馈调节下的。总之，在一个谱系中存在的多个细胞阶段和复杂的反馈调节被认为赋予了组织在细胞数量（组织总体积）和细胞身份（组织中不同细胞类型，特别是TD细胞的比例）方面自动调节发育和再生的能力。在本文中，我们模拟了小鼠嗅上皮（OE）的神经发生，在这个系统中，谱系阶段和控制终分化嗅觉受体神经元（orn）生成的反馈调节介质已经成为许多实验工作的主题。本文讨论了该系统稳态的存在唯一性，以及这些稳态的局部稳定性和全局稳定性。特别是，当负反馈回路被表示为希尔函数或更一般的形式时，我们确定了系统稳定性的参数条件。我们的研究结果表明，两个因素-转运扩增（TA）祖细胞增殖的自动调节和TD细胞的低死亡率-增强了该系统的稳定性。
Studies of developing and self-renewing tissues have shown that differentiated cell types are typically specified through the actions of multistage cell lineages. Such lineages commonly include a stem cell and multiple progenitor (transit amplifying; TA) cell stages, which ultimately give rise to terminally differentiated (TD) cells. In several cases, self-renewal and differentiation of stem and progenitor cells within such lineages have been shown to be under feedback regulation. Together, the existence of multiple cell stages within a lineage and complex feedback regulation are thought to confer upon a tissue the ability to autoregulate development and regeneration, in terms of both cell number (total tissue volume) and cell identity (the proportions of different cell types, especially TD cells, within the tissue). In this paper, we model neurogenesis in the olfactory epithelium (OE) of the mouse, a system in which the lineage stages and mediators of feedback regulation that govern the generation of terminally differentiated olfactory receptor neurons (ORNs) have been the subject of much experimental work. Here we report on the existence and uniqueness of steady states in this system, as well as local and global stability of these steady states. In particular, we identify parameter conditions for the stability of the system when negative feedback loops are represented either as Hill functions, or in more general terms. Our results suggest that two factors – autoregulation of the proliferation of transit amplifying (TA) progenitor cells, and a low death rate of TD cells – enhance the stability of this system.
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