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Mechanochemical feedback loops in contact-dependent fate patterning 接触依赖性命运模式中的机械化学反馈回路
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-01 DOI: 10.1016/j.coisb.2023.100445
T. Dullweber , A. Erzberger

To reliably form and maintain structures with specific functions, many multicellular systems evolved to leverage the interplay between biochemical signaling, mechanics, and morphology.

We review mechanochemical feedback loops in cases where cell–cell contact-based Notch signaling drives fate decisions, and the corresponding differentiation process leads to contact remodeling. We compare different mechanisms for initial symmetry breaking and subsequent pattern refinement, as well as discuss how patterning outcomes depend on the relationship between biochemical and mechanical timescales.

We conclude with an overview of new approaches, including the study of synthetic circuits, and give an outlook on future experimental and theoretical developments toward dissecting and harnessing mechanochemical feedback.

为了可靠地形成和维持具有特定功能的结构,许多多细胞系统进化为利用生物化学信号、力学和形态学之间的相互作用。我们回顾了基于细胞-细胞接触的Notch信号驱动命运决定以及相应的分化过程导致接触重塑的情况下的机械化学反馈回路。我们比较了初始对称性破坏和随后的模式细化的不同机制,并讨论了模式化结果如何取决于生物化学和机械时间尺度之间的关系。最后,我们概述了新的方法,包括合成电路的研究,并展望了未来在分析和利用机械化学反馈方面的实验和理论发展。
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引用次数: 1
Heterogeneity and developmental dynamics of mammalian neocortical progenitors 哺乳动物新皮质祖细胞的异质性和发育动力学
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-01 DOI: 10.1016/j.coisb.2023.100444
Leila Haj Abdullah Alieh, Antonio Herrera, Gioele La Manno

The central nervous system develops from a pool of neural progenitors which, depending on their location and time of division, generate cells committed to differentiate into specific kinds of neurons or glia. In the last decades, the developmental neurobiology field has made important progress in understanding neural cell-type specification: key patterning mechanisms were discovered, the different waves of neurogenesis described, and the dynamics of cortical stratification elucidated. However, only recently, with the advent of single-cell genomics and organoid culturing methods, we were able to measure the transcriptional signatures of individual progenitors systematically and flexibly perturb human development. Together these fine-grained readouts and perturbation possibilities have allowed comparing neural differentiation between species and dissecting the relationship between progenitors' phenotype and fate commitment. This review summarizes recent in vivo and in vitro studies that have contributed to our understanding of temporal progression and coordination of neuronal cell specification across mammals.

中枢神经系统由一群神经祖细胞发育而来,这些神经祖细胞根据其分裂的位置和时间,产生致力于分化为特定类型神经元或神经胶质细胞的细胞。在过去的几十年里,发育神经生物学领域在理解神经细胞类型规范方面取得了重要进展:发现了关键的模式机制,描述了不同的神经发生波,并阐明了皮层分层的动力学。然而,直到最近,随着单细胞基因组学和类器官培养方法的出现,我们才能够系统而灵活地测量个体祖细胞的转录特征,从而干扰人类的发育。结合这些细粒度的读数和扰动可能性,可以比较物种之间的神经分化,并剖析祖细胞表型和命运承诺之间的关系。这篇综述总结了最近的体内和体外研究,这些研究有助于我们理解哺乳动物神经元细胞规格的时间进展和协调。
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引用次数: 0
Eukaryotic gene regulation at equilibrium, or non? 真核生物基因调控是否处于平衡状态?
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100435
Benjamin Zoller , Thomas Gregor , Gašper Tkačik

Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code.

假设转录因子平衡结合的转录调节模型在预测真核生物基因序列表达方面不如在细菌中成功。这可能是由于真核生物调节的非平衡性质。不幸的是,可能的非平衡机制的空间是巨大的,而且主要是无趣的。因此,关键问题是如何有效地导航这个空间,以关注与生物学相关的机制和模型。在这篇综述中,我们提倡理论的规范性作用-理论规定而不仅仅是描述-提供这样一个焦点。理论应该扩展其职权范围,超越从数据中推断机制模型,而应该确定可能已经被进化选择的非平衡基因调控方案,尽管它们消耗能量,因为它们精确、可靠、快速,或者以其他方式优于平衡状态下的调控。我们通过提供模拟代码的玩具示例来说明我们的推理。
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引用次数: 8
Critical phenomena in embryonic organization 胚胎组织中的关键现象
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100433
Camilla Autorino , Nicoletta I. Petridou

The physics of critical points lies behind the organization of various complex systems, from molecules to ecosystems. Several functional benefits emerge when operating at the edge of a critical point, at criticality, potentially explaining the optimality of biological function. Here, we propose that introducing the concept of criticality in developmental biology may explain remarkable features of embryonic development, such as collective behavior and fitness. Recent interdisciplinary studies approached embryonic processes with statistical physics frameworks and revealed that biochemical and biomechanical processes of embryonic development resemble critical phenomena. We discuss those processes, including gene expression, cell differentiation, and tissue mechanics, and challenge if criticality has a beneficial function during embryonic organization.

从分子到生态系统,各种复杂系统的组织背后都隐藏着临界点的物理学原理。当在临界点的边缘操作时,出现了几个功能上的好处,在临界状态下,潜在地解释了生物功能的最佳性。在这里,我们提出在发育生物学中引入临界性的概念可以解释胚胎发育的显著特征,如集体行为和适合度。最近的跨学科研究用统计物理框架来探讨胚胎过程,揭示了胚胎发育的生化和生物力学过程类似于临界现象。我们讨论了这些过程,包括基因表达、细胞分化和组织力学,并挑战临界是否在胚胎组织中具有有益的功能。
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引用次数: 3
Transcription factor binding and activity on chromatin 转录因子在染色质上的结合和活性
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100438
Jorge Trojanowski , Karsten Rippe

The binding of transcription factors (TFs) via their DNA binding domain at gene promoters or enhancers is part of a multi-step process that leads to transcription activation in eukaryotes. The kinetic on- and off-rates of different TF states are governed by a complex interplay of factors that involve chromatin organization on the level of individual nucleosome positions up to actively transcribed chromatin subcompartments on the mesoscale. Furthermore, not only the TF DNA binding domain but also the activation domain affect TF assembly on chromatin. Here, we summarize recent findings on the interplay between TF binding, chromatin organization, and gene activation to highlight features that need to be considered for constructing quantitative models of eukaryotic gene regulation.

转录因子(TFs)通过其DNA结合域在基因启动子或增强子上的结合是导致真核生物转录激活的多步骤过程的一部分。不同TF状态的动力学开断率受多种因素的复杂相互作用控制,这些因素包括单个核小体位置水平上的染色质组织,以及中观尺度上活跃转录的染色质亚室。此外,TF DNA结合域和激活域不仅影响TF在染色质上的组装。在这里,我们总结了最近关于TF结合、染色质组织和基因激活之间相互作用的发现,以突出构建真核生物基因调控定量模型需要考虑的特征。
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引用次数: 4
Nanoscale nuclear environments, fine-scale 3D genome organization and transcription regulation 纳米尺度的核环境,精细尺度的三维基因组组织和转录调控
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100436
Jieru Li, Alexandros Pertsinidis

Decades of in vitro biochemical reconstitution, genetics and structural biology studies have established a vast knowledge base on the molecular mechanisms of chromatin regulation and transcription. A remaining challenge is to understand how these intricate biochemical systems operate in the context of the 3D genome organization and in the crowded and compartmentalized nuclear milieu. Here we review recent progress in this area based on high-resolution imaging approaches.

几十年的体外生化重建、遗传学和结构生物学研究已经建立了染色质调控和转录的分子机制的庞大知识基础。剩下的挑战是了解这些复杂的生化系统如何在三维基因组组织的背景下以及在拥挤和分隔的核环境中运作。本文综述了基于高分辨率成像方法的这一领域的最新进展。
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引用次数: 1
Editorial overview: The metabolic network 编辑概述:代谢网络
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100432
Sarah-Maria Fendt, Markus Ralser
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引用次数: 0
Robust cell identity specifications through transitions in the collective state of growing developmental systems 通过生长发育系统的集体状态的转变,健壮的细胞身份规范
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100437
Angel Stanoev , Aneta Koseska

Mammalian development is characterized with transitions from homogeneous populations of precursor to heterogeneous population of specified cells. We review here the main dynamical mechanisms through which such transitions are conceptualized, and discuss that the differentiation timing, robust cell-type proportions and recovery upon perturbation are emergent property of proliferating and communicating cell populations. We argue that studying developmental systems using transitions in collective system states is necessary to describe observed experimental features, and propose additionally the basis of a novel analytical method to deduce the relationship between single-cell dynamics and the collective, symmetry-broken states in cellular populations.

哺乳动物发育的特点是由同质的前体群体向异质的特定细胞群体过渡。我们在这里回顾了这些转变的主要动力学机制,并讨论了分化时间、稳健的细胞类型比例和扰动后的恢复是增殖和交流细胞群体的紧急特性。我们认为,利用集体系统状态的过渡来研究发育系统对于描述观察到的实验特征是必要的,并提出了一种新的分析方法的基础,以推断单细胞动力学与细胞群体中集体对称破碎状态之间的关系。
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引用次数: 1
The energetics of activator–promoter recognition 激活子-启动子识别的能量学
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/j.coisb.2022.100434
Hinrich Boeger

Eukaryotes and bacteria have evolved entirely different mechanisms to cope with the problem of how to reconcile regulatory specificity in transcription, the recognition of specific DNA sequences by transcriptional activators, with speed, the ability to quickly respond to environmental change. It is argued here that eukaryotes enhance the specificity of activator–promoter recognition via ATP-dependent chromatin remodeling, whereas bacteria employ allosteric effectors to control specific activator–DNA binding reactions.

真核生物和细菌已经进化出完全不同的机制来应对如何协调转录中的调节特异性问题,即转录激活子识别特定DNA序列的速度,以及快速响应环境变化的能力。本文认为真核生物通过依赖atp的染色质重塑来增强激活子-启动子识别的特异性,而细菌则利用变构效应物来控制特定的激活子- dna结合反应。
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引用次数: 0
Editorial Board Page 编委会页面
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-09-01 DOI: 10.1016/S2452-3100(22)00025-7
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Current Opinion in Systems Biology
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