C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells
C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells
复制标题
线虫 Runx/CBFβ 抑制 POP-1 TCF 将干细胞样接缝细胞的不对称分裂转化为增殖分裂
作者：
Suzanne E. M. van der Horst;J. Cravo;A. Woollard;J. Teapal;S. van den Heuvel
摘要细胞增殖和不对称分裂之间的正确平衡是正常发育、干细胞维持和组织稳态的基础。是什么决定了细胞进行对称或不对称的细胞分裂是知之甚少。为了深入了解所涉及的机制，我们研究了秀丽隐杆线虫表皮中的干细胞样缝细胞。接缝细胞经历由不同的经典Wnt/β-连环蛋白信号传导指示的可再现的不对称分裂模式，以及增加接缝细胞数量的对称分裂。使用延时荧光显微镜，我们观察到对称的细胞分裂维持Wnt/β-连环蛋白途径组分的不对称定位。我们的观察，基于谱系特异性敲除和GFP标记的内源性POP-1，支持模型，POP-1 TCF诱导分化在高核水平，而低核POP-1促进缝细胞自我更新。在对称分裂之前，转录调节因子RNT-1 Runx和辅因子BRO-1CBFβ通过下调pop-1表达暂时绕过Wnt/β-catenin不对称。因此，RNT-1/BRO-1似乎使POP-1低于其阻遏物功能所需的水平，这将分化转化为自我更新。因此，我们发现保守的Runx/CBFβ型干细胞调节因子通过对抗TCF相关的转录抑制而将不对称性转换为增殖性细胞分裂。为了将不对称分裂转变为增殖性细胞分裂，C. elegans RNT-1/BRO-1转录抑制因子在缝干细胞中抑制POP-1 TCF表达，这将POP-1诱导的分化转变为自我更新。
ABSTRACT A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1Runx and cofactor BRO-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression. Summary: To switch asymmetric to proliferative cell division, the C. elegans RNT-1/BRO-1 transcriptional repressor opposes POP-1 TCF expression in seam stem cells, which turns POP-1-induced differentiation into self-renewal.
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影响因子：
11.8
作者：
Lin, SY;Johnson, SM;Slack, FJ
通讯作者：
Slack, FJ
影响因子：
56.9
作者：
AMBROS, V;HORVITZ, HR
通讯作者：
HORVITZ, HR
影响因子：
11.8
作者：
Abrahante, JE;Daul, AL;Rougvie, AE
通讯作者：
Rougvie, AE
影响因子：
16
作者：
Slack, FJ;Basson, M;Ruvkun, G
通讯作者：
Ruvkun, G
异时基因形成的时间模式。
DOI：
10.1146/annurev.genet.31.1.611
发表时间：
1997
期刊：
Annual review of genetics.
影响因子：
--
作者：
Slack,F;Ruvkun,G
通讯作者：
Ruvkun,G