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Differentiation最新文献

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NOTCH1, 2, and 3 receptors enhance osteoblastogenesis of mesenchymal C3H10T1/2 cells and inhibit this process in preosteoblastic MC3T3-E1 cells NOTCH1、2和3受体促进间充质C3H10T1/2细胞成骨，抑制成骨前MC3T3-E1细胞成骨。
IF 2.2 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-21 DOI: 10.1016/j.diff.2025.100837
Jose-Luis Resuela-González , María-Julia González-Gómez , María-Milagros Rodríguez-Cano , Susana López-López , Eva-María Monsalve , María-José M. Díaz-Guerra , Jorge Laborda , María-Luisa Nueda , Victoriano Baladrón
Osteoblastogenesis is governed by complex interplays among signaling pathways, which modulate the expression of specific markers at each differentiation stage. This process enables osteoblast precursor cells to adopt the morphological and biochemical characteristics of mature bone cells. Our study investigates the role of NOTCH signaling in osteogenesis in MC3T3-E1 and C3H10T1/2 cell lines. MC3T3-E1 cells are preosteoblast precursors widely recognized as a model for bone biology research, offering a convenient and physiologically relevant system to study osteoblast transcriptional regulation. Conversely, the mesenchymal C3H10T1/2 cells are multipotent, capable of differentiating into osteoblasts, adipocytes, and chondrocytes under specific extracellular cues.
The core of this in vitro study is the comparative analysis of the impact of overexpressing each mammalian NOTCH receptor on osteoblastogenesis in two cell lines reflecting different cell differentiation stages. We generated stable transfectant pools of both cell lines for each of the four NOTCH receptors and characterized their effect on osteoblastogenesis. We successfully obtained transfectant pools that overexpress Notch1, Notch2 and Notch3 at both mRNA and protein levels. However, we were unable to obtain cells overexpressing Notch4 at protein level. Our findings reveal that the overexpression of NOTCH1, NOTCH2, and NOTCH3 receptors promotes osteoblast differentiation in mesenchymal C3H10T1/2 cells, while inhibiting it in preosteoblastic MC3T3-E1 cells. These results provide novel insights into the distinct roles of NOTCH receptors in osteoblastogenesis across two different precursor cell types, potentially guiding the development of new therapeutic approaches for bone diseases.
成骨细胞的形成是由信号通路之间复杂的相互作用所控制的，这些信号通路调节着每个分化阶段特定标记物的表达。这一过程使成骨前体细胞具有成熟骨细胞的形态和生化特征。本研究探讨了NOTCH信号在MC3T3-E1和C3H10T1/2细胞系成骨过程中的作用。MC3T3-E1细胞是成骨细胞前体细胞，被广泛认为是骨生物学研究的模型，为研究成骨细胞转录调控提供了方便和生理相关的系统。相反，间充质C3H10T1/2细胞是多能的，能够在特定的细胞外提示下分化成成骨细胞、脂肪细胞和软骨细胞。本体外研究的核心是对比分析两种反映不同细胞分化阶段的细胞系中过表达每种哺乳动物NOTCH受体对成骨细胞形成的影响。我们为四种NOTCH受体中的每一种生成了稳定的转染池，并表征了它们对成骨细胞发生的影响。我们成功地获得了Notch1、Notch2和Notch3在mRNA和蛋白水平上过表达的转染池。然而，我们无法获得在蛋白水平上过表达Notch4的细胞。我们的研究结果表明，NOTCH1、NOTCH2和NOTCH3受体的过表达促进了间充质C3H10T1/2细胞的成骨细胞分化，而抑制了成骨前MC3T3-E1细胞的成骨分化。这些结果为NOTCH受体在两种不同前体细胞类型的成骨细胞形成中的独特作用提供了新的见解，可能指导骨疾病新治疗方法的发展。
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
Divergent functions of the evolutionarily conserved, yet seemingly dispensable, Wnt target, sp5 进化保守但看似可有可无的 Wnt 靶标 sp5 的不同功能。
IF 2.2 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01 DOI: 10.1016/j.diff.2024.100829
Saurav Mohanty, Arne C. Lekven
The activation of sp5 in response to Wnt/β-catenin signaling is observed in many species during axis patterning, neural crest induction, maintenance and differentiation of stem cells. Indeed, the conserved response of sp5 orthologs to Wnt-mediated activation is the basis for this gene commonly being used as a readout for Wnt signaling activity. However, several seemingly conflicting findings regarding the function of sp5 in the context of Wnt signaling cast this gene in an enigmatic light. In this review, we examine current knowledge of sp5 structure and function, its relationship to Wnt signaling in varied contexts, and present perspectives on how progress on this interesting gene can move forward.
在许多物种的轴形态形成、神经嵴诱导、干细胞的维持和分化过程中，都能观察到 sp5 对 Wnt/β-catenin 信号的激活反应。事实上，sp5 同源物对 Wnt 介导的激活的保守反应是该基因通常被用作 Wnt 信号活动读数的基础。然而，关于 sp5 在 Wnt 信号转导背景下的功能，一些看似相互矛盾的研究结果却让这个基因变得扑朔迷离。在这篇综述中，我们探讨了目前对 sp5 结构和功能的认识、它在不同情况下与 Wnt 信号转导的关系，并就如何推进这一有趣基因的研究提出了自己的观点。
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引用次数: 0
Regulation of trophectoderm morphogenesis by small GTPase RHOA through HIPPO signaling-dependent and -independent mechanisms in mouse preimplantation development 小GTPase RHOA通过HIPPO信号依赖性和非依赖性机制调控小鼠着床前发育的滋养外胚层形态发生。
IF 2.2 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01 DOI: 10.1016/j.diff.2025.100835
Yusuke Marikawa, Vernadeth B. Alarcon
The trophectoderm (TE) is the first tissue to differentiate during the preimplantation development of the mammalian embryo. It forms the outer layer of the blastocyst and is responsible for generating the blastocoel, a fluid-filled cavity whose expansion is essential for successful hatching and implantation. Here, we investigated the role of the small GTPase RHOA in the morphogenesis of the TE, particularly its relationship with HIPPO signaling, using mouse embryos as a model. Inhibition of RHOA resulted in the failure to form a blastocoel and significantly altered the expression of numerous genes. Transcriptomic analysis revealed that 330 genes were down-regulated and 168 genes were up-regulated by more than two-fold. Notably, 98.4% of these transcriptional changes were reversed by simultaneous inhibition of LATS kinases, indicating that the transcriptional influence of RHOA is primarily mediated through HIPPO signaling. Many of the down-regulated genes are involved in critical processes of TE morphogenesis, such as apical-basal cell polarization, tight junction formation, and sodium and water transport, suggesting that RHOA supports TE development by enhancing the expression of morphogenesis-related genes through HIPPO signaling, specifically via TEAD transcription factors. However, RHOA inhibition also disrupted apical-basal polarity and tight junctions, effects that were not restored by LATS inhibition, pointing to additional HIPPO signaling-independent mechanisms by which RHOA controls TE morphogenesis. Furthermore, RHOA inhibition impaired cell viability at the late blastocyst stage, with partial rescue observed upon LATS inhibition, suggesting that RHOA maintains cell survival through both HIPPO signaling-dependent and -independent pathways. A deeper knowledge of the molecular mechanisms governing TE morphogenesis, including blastocoel expansion and cell viability, could significantly advance assisted reproductive technologies aimed at producing healthy blastocysts.
营养外胚层（TE）是哺乳动物胚胎着床前发育过程中最先分化的组织。它形成囊胚的外层，负责产生囊胚腔，囊胚腔是一个充满液体的腔，其扩张对成功孵化和着床至关重要。在这里，我们以小鼠胚胎为模型，研究了小GTPase RHOA在TE形态发生中的作用，特别是它与HIPPO信号传导的关系。RHOA的抑制导致囊胚不能形成，并显著改变了许多基因的表达。转录组学分析显示，330个基因下调，168个基因上调2倍以上。值得注意的是，98.4%的这些转录变化通过同时抑制LATS激酶而逆转，这表明RHOA的转录影响主要是通过HIPPO信号传导介导的。许多下调的基因参与TE形态发生的关键过程，如尖-基底细胞极化、紧密连接的形成以及钠和水的运输，这表明RHOA通过HIPPO信号，特别是通过TEAD转录因子，通过增强形态发生相关基因的表达来支持TE的发展。然而，RHOA抑制也破坏了根尖极性和紧密连接，而LATS抑制无法恢复这种影响，这表明RHOA控制TE形态发生的另外一种与HIPPO信号无关的机制。此外，RHOA抑制会损害囊胚后期的细胞活力，在LATS抑制下观察到部分恢复，这表明RHOA通过HIPPO信号依赖性和非依赖性途径维持细胞存活。更深入地了解TE形态发生的分子机制，包括囊胚膨胀和细胞活力，可以显著推进旨在产生健康囊胚的辅助生殖技术。
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
IF 2.6 3区 生物学 Q4 CELL BIOLOGY
Differentiation
Pub Date : 2025-01-01
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引用次数: 0
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