Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response.
Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response.
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转录因子波动是信号通路反应中细胞间变异的基础。
DOI：
10.1093/genetics/iyad094
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发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Cohen,BarakA
中科院分区：
文献类型：
--
作者：
Ramu,Avinash;Cohen,BarakA
克隆细胞之间的随机差异可以在发育中启动细胞命运决定，或者在对药物或细胞外配体的反应中引起细胞间差异。一种假设是，这种表型变异的一些是由转录因子（TF）的活性的随机波动引起的。我们在NIH 3 T3-CG细胞中使用对Hedgehog信号传导的响应作为模型细胞响应来测试这一假设。在这里，我们提出的证据表明，在NIH 3 T3-CG细胞中存在不同的快速和缓慢反应的亚状态。这两个亚状态有不同的表达谱，在thePrrx 1 TF的波动的基础上的一些差异的表达和反应快，慢细胞。我们的研究结果表明，TF的波动可以导致Hedgehog信号传导的细胞间差异。
Stochastic differences among clonal cells can initiate cell fate decisions in development or cause cell-to-cell differences in the responses to drugs or extracellular ligands. One hypothesis is that some of this phenotypic variability is caused by stochastic fluctuations in the activities of transcription factors (TFs). We tested this hypothesis in NIH3T3-CG cells using the response to Hedgehog signaling as a model cellular response. Here, we present evidence for the existence of distinct fast- and slow-responding substates in NIH3T3-CG cells. These two substates have distinct expression profiles, and fluctuations in thePrrx1TF underlie some of the differences in expression and responsiveness between fast and slow cells. Our results show that fluctuations in TFs can contribute to cell-to-cell differences in Hedgehog signaling.