体细胞与生殖干细胞中 JAK/STAT 信号传导的计算模拟。

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY
Willis X. Li
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引用次数: 0

摘要

背景:Janus 激酶/信号转导和转录激活因子(JAK/STAT)信号通路调节多种细胞过程。该通路中的一个主要活化过程是 STAT 的一个酪氨酸发生磷酸化,将未磷酸化的 STAT(uSTAT)转化为磷酸化的 STAT(pSTAT),后者是一种活性转录因子。在非规范作用中,uSTAT 有助于维持异染色质的稳定性。因此,正如在果蝇体细胞组织中观察到的那样,pSTAT 的增加会同时减少 uSTAT,导致异染色质丢失。与此相反,果蝇雄性生殖干细胞(GSCs)中却出现了相反的现象,由于配体的持续供应,JAK/STAT通路在GSCs中保持持续活跃。在这里,我们利用计算模拟来剖析不同细胞环境下的JAK/STAT通路激活,模拟体细胞和生殖细胞。在这些模拟中,利用常微分方程复制了不同条件下支配 JAK/STAT 信号传导的化学反应:结果表明,体细胞组织中典型的瞬时配体刺激会导致uSTAT水平瞬间下降。相反,配体的持续刺激(GSC 龛的一个特征)导致uSTAT 水平在平衡状态下升高:模拟结果表明,配体暴露的持续时间可以解释在体细胞和GSC中观察到的JAK/STAT激活对异染色质的相反影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Computational simulation of JAK/STAT signaling in somatic versus germline stem cells

Background

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway regulates a variety of cellular processes. A major activation event in this pathway involves the phosphorylation of a tyrosine of STAT, converting unphosphorylated STAT (uSTAT) to phosphorylated STAT (pSTAT), an active transcription factor. In a noncanonical role, uSTAT contributes to the maintenance of heterochromatin stability. As such, an increase in pSTAT concurrently reduces uSTAT, resulting in heterochromatin loss, as observed in Drosophila somatic tissues. Paradoxically, an opposing phenomenon occurs in Drosophila male germline stem cells (GSCs), where the JAK/STAT pathway remains persistently active due to a continuous supply of ligands. Here, computational simulations were employed to dissect JAK/STAT pathway activation under different cellular contexts, mimicking somatic and germline cells. In these simulations, ordinary differential equations were leveraged to replicate the chemical reactions governing JAK/STAT signaling under different conditions.

Results

The outcomes indicate that transient ligand stimulation, typical in somatic tissues, led to a momentary reduction in uSTAT levels. Conversely, sustained ligand stimulation, a characteristic feature of the GSC niche, resulted in elevated uSTAT levels at equilibrium.

Conclusion

The simulation suggests that the duration of ligand exposure could explain the observed opposite effects of JAK/STAT activation on heterochromatin in somatic versus GSCs.

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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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