Mitra Mithun, Batista Sandra L, Coller Hilary A
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Nat Cell Biol. 2025 Jan;27(1):14-27. doi: 10.1038/s41556-024-01582-w. Epub 2025 Jan 9.
Many of the cells in mammalian tissues are in a reversible quiescent state; they are not dividing, but retain the ability to proliferate in response to extracellular signals. Quiescence relies on the activities of transcription factors (TFs) that orchestrate the repression of genes that promote proliferation and establish a quiescence-specific gene expression program. Here we discuss how the coordinated activities of TFs in different quiescent stem cells and differentiated cells maintain reversible cell cycle arrest and establish cell-protective signalling pathways. We further cover the emerging mechanisms governing the dysregulation of quiescence TF networks with age. We explore how recent developments in single-cell technologies have enhanced our understanding of quiescence heterogeneity and gene regulatory networks. We further discuss how TFs and their activities are themselves regulated at the RNA, protein and chromatin levels. Finally, we summarize the challenges associated with defining TF networks in quiescent cells.
哺乳动物组织中的许多细胞处于可逆的静止状态；它们不进行分裂，但保留了响应细胞外信号而增殖的能力。静止状态依赖于转录因子（TFs）的活性，这些转录因子协调抑制促进增殖的基因，并建立特定于静止状态的基因表达程序。在这里，我们讨论不同静止干细胞和分化细胞中转录因子的协同活动如何维持可逆的细胞周期停滞并建立细胞保护信号通路。我们还将探讨随着年龄增长导致静止转录因子网络失调的新出现机制。我们将探索单细胞技术的最新进展如何增进我们对静止异质性和基因调控网络的理解。我们还将讨论转录因子及其活性在RNA、蛋白质和染色质水平上是如何被调控的。最后，我们总结了在定义静止细胞中转录因子网络方面所面临的挑战。
