A systems view of cellular heterogeneity: Unlocking the "wheel of fate".

Cell systems Pub Date : 2025-06-02 DOI:10.1016/j.cels.2025.101300

Hourieh Movasat, Enzo Giacopino, Ali Shahdoost, Yeganeh Dorri Nokoorani, Ali Houshyar Abrbekouh, Yaser Tahamtani, Nika Shakiba

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Abstract

Systems biology offers a view of the cell as an input-output device: a biochemical network (or cellular "processor") that interprets cues from the microenvironment to drive cell fate. Advancements in single-cell technologies are unlocking the cellular black box, revealing heterogeneity in seemingly homogeneous cell populations. But are these differences technical variability or biology? In this review, we explore this question through a systems biology lens, offering a framework for conceptualizing heterogeneity from the cell's perspective and summarizing systems and synthetic biology tools for capturing heterogeneity. While cellular inputs shape the probability of attaining particular fates, each cell spins a stochastic "wheel of fate." Applying this framework, we explore heterogeneity in two case studies: human pluripotent stem cell (hPSC) culture and beta cell differentiation. Looking forward, we discuss how a systems approach to heterogeneity may enable more predictable outcomes in stem cell research, with broad implications for developmental biology and regenerative medicine.

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细胞异质性的系统观点：解开“命运之轮”。

系统生物学将细胞视为一个输入输出设备：一个生化网络（或细胞“处理器”），它解释来自微环境的线索，从而驱动细胞的命运。单细胞技术的进步正在解开细胞黑箱，揭示看似同质的细胞群体的异质性。但这些差异是技术上的变异性还是生物学上的？在这篇综述中，我们通过系统生物学的视角探讨了这个问题，提供了一个从细胞角度概念化异质性的框架，并总结了捕获异质性的系统和合成生物学工具。当细胞输入决定获得特定命运的概率时，每个细胞都在旋转一个随机的“命运之轮”。应用这一框架，我们在两个案例研究中探索异质性：人类多能干细胞（hPSC）培养和β细胞分化。展望未来，我们讨论了异质性的系统方法如何在干细胞研究中实现更可预测的结果，这对发育生物学和再生医学具有广泛的意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Cell systems

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