Cell division

细胞分裂
  • 文章类型: Journal Article
    非编码RNA(ncRNAs)是一个异质组,在结构和序列长度方面,由不编码蛋白质的RNA分子组成。这些ncRNAs在基因表达的调控中起着核心作用,并且几乎参与了所分析的每个过程,确保细胞内稳态。虽然,多年来,许多研究集中在核起源的非编码转录物的表征上,改进的生物信息学工具和下一代测序(NGS)平台已经允许鉴定数百种从线粒体基因组转录的ncRNA(mt-ncRNA),包括长链非编码RNA(lncRNA),环状RNA,和microRNA(miR)。Mt-ncRNAs已经在不同的细胞过程中被描述,如线粒体蛋白质组稳态和逆行信号传导;然而,大多数mt-ncRNAs的功能仍然未知。这篇综述集中于人类mt-ncRNAs的一个亚组,其功能障碍与细胞周期调节的失败有关。导致细胞生长缺陷,细胞增殖,和细胞凋亡,和肿瘤标志的发展,如细胞迁移和转移形成,从而促进癌的发生和肿瘤的发展。在这里,我们提供了mt-ncRNAs/癌症关系的概述,这可能有助于肿瘤学领域新的生物医学应用的未来发展。
    Non-coding RNAs (ncRNAs) are a heterogeneous group, in terms of structure and sequence length, consisting of RNA molecules that do not code for proteins. These ncRNAs have a central role in the regulation of gene expression and are virtually involved in every process analyzed, ensuring cellular homeostasis. Although, over the years, much research has focused on the characterization of non-coding transcripts of nuclear origin, improved bioinformatic tools and next-generation sequencing (NGS) platforms have allowed the identification of hundreds of ncRNAs transcribed from the mitochondrial genome (mt-ncRNA), including long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miR). Mt-ncRNAs have been described in diverse cellular processes such as mitochondrial proteome homeostasis and retrograde signaling; however, the function of the majority of mt-ncRNAs remains unknown. This review focuses on a subgroup of human mt-ncRNAs whose dysfunction is associated with both failures in cell cycle regulation, leading to defects in cell growth, cell proliferation, and apoptosis, and the development of tumor hallmarks, such as cell migration and metastasis formation, thus contributing to carcinogenesis and tumor development. Here we provide an overview of the mt-ncRNAs/cancer relationship that could help the future development of new biomedical applications in the field of oncology.
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  • 文章类型: Journal Article
    柿子(DiospyroskakiThunb。)果实大小变化丰富。研究柿子果实的大小有助于提高其经济价值。目前,柿子果实大小形成的调控机制尚不清楚。在这项研究中,通过形态学研究了果实大小形成的机理,细胞学和转录组学分析,以及使用“Yaoxianwuhua”的大果实和小果实进行的外源乙烯和氨基乙氧基甘氨酸(AVG:乙烯抑制剂)实验。结果表明,3-4阶段(6月11日至6月25日)是柿子大果和小果分化的关键形态时期。在这个关键的形态学时期,大果实中的细胞数量明显多于小果实中的细胞数量,说明细胞数量的差异是柿子果实大小分化的主要原因。细胞数量的差异是由细胞分裂引起的。CNR1,ANT,LAC17和EB1C,与细胞分裂有关,可能参与调节柿子果实的大小。外源性乙酮导致水果重量减少,和AVG治疗有相反的效果。此外,LAC17和ERF114在乙素治疗后上调。这些结果表明,高乙烯水平可以降低柿子果实的大小,可能是通过抑制细胞分裂.本研究为理解柿子果实大小的调控机制提供了有价值的信息,为后续育种和人工调控果实大小奠定了基础。
    Persimmon (Diospyros kaki Thunb.) fruit size variation is abundant. Studying the size of the persimmon fruit is helpful in improving its economic value. At present, the regulatory mechanism of persimmon fruit size formation is still unclear. In this study, the mechanism of fruit size formation was investigated through morphological, cytological and transcriptomic analyses, as well as exogenous ethrel and aminoethoxyinylglycine (AVG: ethylene inhibitor) experiments using the large fruit and small fruit of \'Yaoxianwuhua\'. The results showed that stages 3-4 (June 11-June 25) are the crucial morphological period for differentiation of large fruit and small fruit in persimmon. At this crucial morphological period, the cell number in large fruit was significantly more than that in small fruit, indicating that the difference in cell number is the main reason for the differentiation of persimmon fruit size. The difference in cell number was caused by cell division. CNR1, ANT, LAC17 and EB1C, associated with cell division, may be involved in regulating persimmon fruit size. Exogenous ethrel resulted in a decrease in fruit weight, and AVG treatment had the opposite effect. In addition, LAC17 and ERF114 were upregulated after ethrel treatment. These results indicated that high ethylene levels can reduce persimmon fruit size, possibly by inhibiting cell division. This study provides valuable information for understanding the regulation mechanism of persimmon fruit size and lays a foundation for subsequent breeding and artificial regulation of fruit size.
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  • 文章类型: Journal Article
    弓形虫,一种重要的机会病原体,强调开发新的治疗药物和确定新的药物靶点的必要性。我们的发现表明,KU60019和CP466722(缩写为KU和CP)对弓形虫的半最大抑制浓度(IC50)为0.522μM和0.702μM,分别,选择指数(SI)为68和10。用KU和CP处理影响弓形虫的体外生长,在子寄生虫中诱导异常分裂。透射电子显微镜显示KU和CP提示弓形虫异常分裂,伴随着细胞增大,核收缩,和增加的致密颗粒密度,提示寄生虫囊泡运输的潜在损害。随后的研究揭示了它们调节弓形虫中某些分泌蛋白和FASII(II型脂肪酸合成)表达的能力,以及包括自噬相关蛋白ATG8(自噬相关蛋白8)的点状聚集,从而加速程序性死亡。利用DARTS(药物亲和力反应靶标稳定性)与4D-Label-free定量蛋白质组学技术,我们确定了七种与KU结合的靶蛋白,涉及关键的生物过程,如脂肪酸代谢,线粒体ATP传递,微管形成,弓形虫中的高尔基蛋白转运。分子对接预测它们良好的结合亲和力。此外,KU对感染弓形虫的小鼠有轻微的保护作用。阐明这些靶蛋白的功能及其与ATM激酶抑制剂的作用机制可能潜在地增强弓形虫病的治疗范例。
    Toxoplasma gondii, an important opportunistic pathogen, underscores the necessity of developing novel therapeutic drugs and identifying new drug targets. Our findings indicate that the half-maximal inhibitory concentrations (IC50) of KU60019 and CP466722 (abbreviated as KU and CP) against T. gondii are 0.522 μM and 0.702 μM, respectively, with selection indices (SI) of 68 and 10. Treatment with KU and CP affects the in vitro growth of T. gondii, inducing aberrant division in the daughter parasites. Transmission electron microscopy reveals that KU and CP prompt the anomalous division of T. gondii, accompanied by cellular enlargement, nuclear shrinkage, and an increased dense granule density, suggesting potential damage to parasite vesicle transport. Subsequent investigations unveil their ability to modulate the expression of certain secreted proteins and FAS II (type II fatty acid synthesis) in T. gondii, as well as including the dot-like aggregation of the autophagy-related protein ATG8 (autophagy-related protein 8), thereby expediting programmed death. Leveraging DARTS (drug affinity responsive target stability) in conjunction with 4D-Label-free quantitative proteomics technology, we identified seven target proteins binding to KU, implicated in pivotal biological processes such as the fatty acid metabolism, mitochondrial ATP transmission, microtubule formation, and Golgi proteins transport in T. gondii. Molecular docking predicts their good binding affinity. Furthermore, KU has a slight protective effect on mice infected with T. gondii. Elucidating the function of those target proteins and their mechanism of action with ATM kinase inhibitors may potentially enhance the treatment paradigm for toxoplasmosis.
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  • 文章类型: Journal Article
    肌动球蛋白皮质是通过细胞骨架重塑产生驱动形状变化的力的活性材料。细胞分裂是重要的细胞分裂事件,在此期间皮质肌动球蛋白环关闭以分离两个子细胞。我们的主动凝胶理论预测,由生化振荡器控制并经历机械应变的肌动球蛋白系统将表现出复杂的时空行为。为了测试体内活性材料是否表现出时空复杂的动力学,我们以前所未有的时间分辨率对秀丽隐杆线虫胚胎进行成像,并发现细胞动力学皮质部分经历了加速和减速的周期性阶段。收缩振荡表现出一系列周期性,包括那些比RhoA脉冲的时间尺度长得多的周期,胞质分裂比任何其他生物学背景都短。在体内或计算机上修改机械反馈表明,收缩振荡的时间随机械反馈的强度而延长。在速度振荡周期较长的情况下,会发生快速局部振铃,可能是由于局部应力增加,因此,机械反馈。在材料周转率很高的地方也会发生快速侵入,在体内和硅。我们建议在脉冲RhoA活性引发的下游,机械反馈,包括但不限于材料平流,将收缩性的时间尺度扩展到生化输入的时间尺度之外,因此,使其对激活的波动具有鲁棒性。尽管需要从压实中恢复细胞骨架重塑,但收缩性的周向传播可能允许持续的收缩性。因此,比如生化反馈,机械反馈提供活性材料的响应性和鲁棒性。
    The actomyosin cortex is an active material that generates force to drive shape changes via cytoskeletal remodeling. Cytokinesis is the essential cell division event during which a cortical actomyosin ring closes to separate two daughter cells. Our active gel theory predicted that actomyosin systems controlled by a biochemical oscillator and experiencing mechanical strain would exhibit complex spatiotemporal behavior. To test whether active materials in vivo exhibit spatiotemporally complex kinetics, we imaged the C. elegans embryo with unprecedented temporal resolution and discovered that sections of the cytokinetic cortex undergo periodic phases of acceleration and deceleration. Contractile oscillations exhibited a range of periodicities, including those much longer periods than the timescale of RhoA pulses, which was shorter in cytokinesis than in any other biological context. Modifying mechanical feedback in vivo or in silico revealed that the period of contractile oscillation is prolonged as a function of the intensity of mechanical feedback. Fast local ring ingression occurs where speed oscillations have long periods, likely due to increased local stresses and, therefore, mechanical feedback. Fast ingression also occurs where material turnover is high, in vivo and in silico. We propose that downstream of initiation by pulsed RhoA activity, mechanical feedback, including but not limited to material advection, extends the timescale of contractility beyond that of biochemical input and, therefore, makes it robust to fluctuations in activation. Circumferential propagation of contractility likely allows for sustained contractility despite cytoskeletal remodeling necessary to recover from compaction. Thus, like biochemical feedback, mechanical feedback affords active materials responsiveness and robustness.
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  • 文章类型: Journal Article
    尽管在植物细胞分裂过程中新壁的形成倾向于遵循最大拉伸应力方向,随着时间的推移,对单个细胞的分析揭示了一种更加多变的行为。迄今为止,这种变异性的起源以及细胞分裂前相间微管行为的确切作用仍然是神秘的。为了解决这个问题,我们利用了拟南芥的茎,其中拉伸应力模式是高度各向异性和稳定的。尽管皮质微管(CMT)通常与最大拉伸应力对齐,我们检测到一个特定的时间窗口,CA.细胞分裂前3小时,其中细胞形成CMT的放射状模式。这种微管阵列组织先于前期带(PPB)形成,预测未来分割平面位置的瞬态CMT阵列。在不同的生长条件下观察到,与细胞几何形状或极性生长素转运无关。有趣的是,这种皮质放射状模式与有据可查的细胞分裂前细胞质微管积累的增加相关.这种放射状组织在trm678突变体的细胞中延长,其中CMT无法形成PPB。而trm678中的划分平面方向更嘈杂,我们发现细胞分裂对称性在子细胞之间的差异较小。我们建议此“径向步长”反映了两个基本细胞分裂属性的鲁棒性权衡:对称性和方向性。这涉及G2中的“重置”阶段,其中细胞质微管积累的增加会暂时破坏CMT与组织应激的对齐。
    Although the formation of new walls during plant cell division tends to follow maximal tensile stress direction, analyses of individual cells over time reveal a much more variable behavior. The origin of such variability as well as the exact role of interphasic microtubule behavior before cell division have remained mysterious so far. To approach this question, we took advantage of the Arabidopsis stem, where the tensile stress pattern is both highly anisotropic and stable. Although cortical microtubules (CMTs) generally align with maximal tensile stress, we detected a specific time window, ca. 3 h before cell division, where cells form a radial pattern of CMTs. This microtubule array organization preceded preprophase band (PPB) formation, a transient CMT array predicting the position of the future division plane. It was observed under different growth conditions and was not related to cell geometry or polar auxin transport. Interestingly, this cortical radial pattern correlated with the well-documented increase of cytoplasmic microtubule accumulation before cell division. This radial organization was prolonged in cells of the trm678 mutant, where CMTs are unable to form a PPB. Whereas division plane orientation in trm678 is noisier, we found that cell division symmetry was in contrast less variable between daughter cells. We propose that this \"radial step\" reflects a trade-off in robustness for two essential cell division attributes: symmetry and orientation. This involves a \"reset\" stage in G2, where an increased cytoplasmic microtubule accumulation transiently disrupts CMT alignment with tissue stress.
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  • 文章类型: Journal Article
    结论:我们研究了拟南芥雌蕊发育过程中D3型细胞周期蛋白的功能,以及它们与激素细胞分裂素和转录因子SPATULA的关系。通过分生组织中的细胞分裂和分化过程来维持植物整个生命的生长。在拟南芥中,gynoecium的发育意味着一个多阶段的过程,在这个过程中,授粉所需的组织,受精,和种子发育形式。CarpelMargin分生组织(CMM)是一团未分化的细胞,可产生雌蕊内部组织,比如隔膜,胚珠,胎盘,真菌,发射道,风格,和耻辱。不同的遗传和荷尔蒙因素,包括细胞分裂素,控制CMM功能。细胞分裂素通过激活细胞周期调节因子作为细胞周期蛋白基因来调节细胞周期转换。D3型细胞周期蛋白在增殖组织中表达,有利于有丝分裂细胞周期而不是核内复制。尽管细胞分裂素在CMM和绞股蓝发育中的作用被高度研究,其在该组织中调节细胞周期的具体作用尚不清楚。此外,尽管对CYCD3基因与细胞分裂素之间的关系进行了广泛的研究,连接它们的监管机制仍然难以捉摸。这里,我们发现D3型细胞周期蛋白在增殖性内侧和外侧组织中表达。相反,这三个CYCD3基因的耗竭表明它们对于绞股蓝的发育不是必需的。然而,外源性细胞分裂素的添加表明,它们可以控制绞股蓝内部组织和外植体的分裂/分化平衡。最后,我们发现SPATULA可能是细胞分裂素和D3型细胞周期蛋白之间的机械联系。数据表明,D3型细胞周期蛋白在雌蕊发育中的作用与细胞分裂素反应有关,它们可能被转录因子SPATULA激活。
    CONCLUSIONS: We studied the D3-type cyclin function during gynoecium development in Arabidopsis and how they are related to the hormone cytokinin and the transcription factor SPATULA. Growth throughout the life of plants is sustained by cell division and differentiation processes in meristematic tissues. In Arabidopsis, gynoecium development implies a multiphasic process where the tissues required for pollination, fertilization, and seed development form. The Carpel Margin Meristem (CMM) is a mass of undifferentiated cells that gives rise to the gynoecium internal tissues, such as septum, ovules, placenta, funiculus, transmitting tract, style, and stigma. Different genetic and hormonal factors, including cytokinin, control the CMM function. Cytokinin regulates the cell cycle transitions through the activation of cell cycle regulators as cyclin genes. D3-type cyclins are expressed in proliferative tissues, favoring the mitotic cell cycle over the endoreduplication. Though the role of cytokinin in CMM and gynoecium development is highly studied, its specific role in regulating the cell cycle in this tissue remains unclear. Additionally, despite extensive research on the relationship between CYCD3 genes and cytokinin, the regulatory mechanism that connects them remains elusive. Here, we found that D3-type cyclins are expressed in proliferative medial and lateral tissues. Conversely, the depletion of the three CYCD3 genes showed that they are not essential for gynoecium development. However, the addition of exogenous cytokinin showed that they could control the division/differentiation balance in gynoecium internal tissues and outgrowths. Finally, we found that SPATULA can be a mechanistic link between cytokinin and the D3-type cyclins. The data suggest that the role of D3-type cyclins in gynoecium development is related to the cytokinin response, and they might be activated by the transcription factor SPATULA.
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  • 文章类型: Journal Article
    对羟基苯甲酸丙酯(PrP)和对羟基苯甲酸二氯丙酯(diClPrP)存在于世界各地的土壤中,主要是由于城市污泥在作物土壤中的掺入以及使用非原废水进行灌溉。关于PrP对植物的不利影响的研究是初期的,对于diClPrP尚未发现。以4、40和400µg/L的浓度评估PrP和diClPrP对洋葱种子的植物毒性潜力,黄瓜(黄瓜),番茄(番茄),和Lactucasativa(生菜),和细胞毒性,基因毒性潜能,并在A.cepa球茎的根分生组织中产生氧反应物质。PrP和diClPrP导致所有四个物种的种子根伸长显着降低。在A.cepa球茎根中,PrP和diClPrP导致较高的前期指数;此外,400µg/L的PrP和三种浓度的diClPrP显着降低了细胞增殖,并引起了大量细胞的改变。此外,diClPrP浓度诱导洋葱鳞茎中钩根的发育。这两种化合物引起过氧化氢酶调节的显著变化,抗坏血酸过氧化物酶,和愈创木酚过氧化物酶,解除根分生组织对抗羟基自由基和超氧化物。因此,PrP和diClPrP对测试物种具有植物毒性和细胞遗传毒性,证明对植物是危险的。
    Propylparaben (PrP) and dichloropropylparaben (diClPrP) are found in soil worldwide, mainly due to the incorporation of urban sludge in crop soils and the use of non-raw wastewater for irrigation. Studies on the adverse effects of PrP on plants are incipient and not found for diClPrP. PrP and diClPrP were evaluated at concentrations 4, 40, and 400 µg/L for their phytotoxic potential to seeds of Allium cepa (onion), Cucumis sativus (cucumber), Lycopersicum sculentum (tomato), and Lactuca sativa (lettuce), and cytotoxic, genotoxic potential, and for generating oxygen-reactive substances in root meristems of A. cepa bulbs. PrP and diClPrP caused a significant reduction in seed root elongation in all four species. In A. cepa bulb roots, PrP and diClPrP resulted in a high prophase index; in addition, PrP at 400 µg/L and diClPrP at the three concentrations significantly decreased cell proliferation and caused alterations in a significant number of cells. Furthermore, diClPrP concentrations induced the development of hooked roots in onion bulbs. The two chemical compounds caused significant changes in the modulation of catalase, ascorbate peroxidase, and guaiacol peroxidase, disarming the root meristems against hydroxyl radicals and superoxides. Therefore, PrP and diClPrP were phytotoxic and cytogenotoxic to the species tested, proving dangerous to plants.
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  • 文章类型: Journal Article
    在生物体中,分裂是细胞存活和将可遗传信息传递给下一代所必需的。出于这个原因,细胞分裂在真核生物和原核生物中高度保守。真核生物中最高度保守的细胞分裂蛋白是微管蛋白和肌动蛋白。微管蛋白聚合形成微管,在真核生物中组装成细胞骨架结构,例如有丝分裂纺锤体在有丝分裂期间将染色单体分开。肌动蛋白聚合形成真核细胞的形态框架,或细胞骨架,在有丝分裂期间经历重组。在原核生物中,两种最高度保守的细胞分裂蛋白是微管蛋白同源物FtsZ和肌动蛋白同源物FtsA。在这一章中,细菌细胞分裂必需蛋白FtsZ和FtsA的功能及其在隔膜分裂体组装中的作用,细胞分裂的部位,将讨论。在大多数细菌中,包括大肠杆菌,微管蛋白同源物FtsZ在中细胞聚合,这一步对于许多其他蛋白质募集到分裂位点至关重要。出于这个原因,FtsZ丰度和聚合都受到多种蛋白质的严格调控。肌动蛋白样FtsA蛋白聚合并将FtsZ聚合物束缚到细胞质膜上。此外,FtsA与后期细胞分裂蛋白相互作用,这对于分裂和在隔膜处建立新的细胞壁至关重要。最近的研究已经调查了FtsA在脂质膜上的肌动蛋白样聚合如何影响分裂,我们将讨论通过FtsZ和FtsA调节细菌分裂的这种方式和其他方式。
    Across living organisms, division is necessary for cell survival and passing heritable information to the next generation. For this reason, cell division is highly conserved among eukaryotes and prokaryotes. Among the most highly conserved cell division proteins in eukaryotes are tubulin and actin. Tubulin polymerizes to form microtubules, which assemble into cytoskeletal structures in eukaryotes, such as the mitotic spindle that pulls chromatids apart during mitosis. Actin polymerizes to form a morphological framework for the eukaryotic cell, or cytoskeleton, that undergoes reorganization during mitosis. In prokaryotes, two of the most highly conserved cell division proteins are the tubulin homolog FtsZ and the actin homolog FtsA. In this chapter, the functions of the essential bacterial cell division proteins FtsZ and FtsA and their roles in assembly of the divisome at the septum, the site of cell division, will be discussed. In most bacteria, including Escherichia coli, the tubulin homolog FtsZ polymerizes at midcell, and this step is crucial for recruitment of many other proteins to the division site. For this reason, both FtsZ abundance and polymerization are tightly regulated by a variety of proteins. The actin-like FtsA protein polymerizes and tethers FtsZ polymers to the cytoplasmic membrane. Additionally, FtsA interacts with later stage cell division proteins, which are essential for division and for building the new cell wall at the septum. Recent studies have investigated how actin-like polymerization of FtsA on the lipid membrane may impact division, and we will discuss this and other ways that division in bacteria is regulated through FtsZ and FtsA.
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  • 文章类型: Journal Article
    背景:最近开发的空间谱系追踪技术在生长细胞群体中的特定基因组基因座处诱导体细胞突变,然后测量采样细胞中的这些突变以及细胞的物理位置。这些技术能够在空间和时间上对发育过程进行高通量研究。然而,这些应用依赖于描述过去细胞分裂和细胞位置的空间细胞谱系树的精确重建。空间谱系树与系统地理学模型有关,这些模型在系统遗传学文献中得到了充分研究。我们证明了基于布朗运动的标准系统地理学模型不足以描述细胞分裂过程中细胞的空间对称位移(SD)。
    结果:我们引入了一种新模型-细胞运动性的SD模型,该模型包括子细胞从亲本细胞的对称位移,然后子细胞的独立扩散。我们表明,该模型更准确地描述了小鼠胚胎干细胞的真实空间谱系追踪中细胞的位置。将空间SD模型与DNA突变的进化模型相结合,我们获得了用于空间谱系追踪的系统地理学模型。使用这个模型,我们设计了一个最大似然框架-MOLLUSC(使用单细胞空间谱系跟踪数据的谱系和位置的最大似然估计)-以共同估计时间分辨的分支长度,空间扩散速率,和突变率。在模拟和真实数据上,我们证明了MOLLUSC准确地估计了所有参数。相比之下,布朗运动模型高估了所有测试用例的空间扩散率。此外,与单独的序列数据相比,包含空间信息提高了分支长度估计的准确性。在真实数据上,我们证明了空间信息比序列数据具有更多的信号用于分支长度估计,建议使用空间信息增强谱系追踪技术对于克服发育系统中基因组编辑的局限性很有用。
    方法:MOLLUSC的python实现可在https://github.com/raphael-group/MOLLUSC获得。
    BACKGROUND: Recently developed spatial lineage tracing technologies induce somatic mutations at specific genomic loci in a population of growing cells and then measure these mutations in the sampled cells along with the physical locations of the cells. These technologies enable high-throughput studies of developmental processes over space and time. However, these applications rely on accurate reconstruction of a spatial cell lineage tree describing both past cell divisions and cell locations. Spatial lineage trees are related to phylogeographic models that have been well-studied in the phylogenetics literature. We demonstrate that standard phylogeographic models based on Brownian motion are inadequate to describe the spatial symmetric displacement (SD) of cells during cell division.
    RESULTS: We introduce a new model-the SD model for cell motility that includes symmetric displacements of daughter cells from the parental cell followed by independent diffusion of daughter cells. We show that this model more accurately describes the locations of cells in a real spatial lineage tracing of mouse embryonic stem cells. Combining the spatial SD model with an evolutionary model of DNA mutations, we obtain a phylogeographic model for spatial lineage tracing. Using this model, we devise a maximum likelihood framework-MOLLUSC (Maximum Likelihood Estimation Of Lineage and Location Using Single-Cell Spatial Lineage tracing Data)-to co-estimate time-resolved branch lengths, spatial diffusion rate, and mutation rate. On both simulated and real data, we show that MOLLUSC accurately estimates all parameters. In contrast, the Brownian motion model overestimates spatial diffusion rate in all test cases. In addition, the inclusion of spatial information improves accuracy of branch length estimation compared to sequence data alone. On real data, we show that spatial information has more signal than sequence data for branch length estimation, suggesting augmenting lineage tracing technologies with spatial information is useful to overcome the limitations of genome-editing in developmental systems.
    METHODS: The python implementation of MOLLUSC is available at https://github.com/raphael-group/MOLLUSC.
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  • 文章类型: Journal Article
    中心体是动物细胞中主要的微管组织中心,核心有一对中心体。它们在间期为纤毛模板,并帮助组织有丝分裂纺锤体,以实现更有效的细胞分裂。这里,我们回顾了中心体在早期发育小鼠和器官形成过程中的作用。哺乳动物细胞通过激活有丝分裂监测途径对中心体功能丧失作出反应,一种定时机制,当超过定义的有丝分裂持续时间时,导致后代p53依赖性细胞死亡。没有中心粒的小鼠胚胎对该途径高度敏感,并在妊娠中期经历胚胎停滞。与其他中心体蛋白相比,中心体核心的完全丧失导致更早和更严重的表型。最后,不同的发育组织具有不同的阈值,并对超出原始胚层的中心粒损失产生分级反应。
    Centrosomes are dominant microtubule organizing centers in animal cells with a pair of centrioles at their core. They template cilia during interphase and help organize the mitotic spindle for a more efficient cell division. Here, we review the roles of centrosomes in the early developing mouse and during organ formation. Mammalian cells respond to centrosome loss-of-function by activating the mitotic surveillance pathway, a timing mechanism that, when a defined mitotic duration is exceeded, leads to p53-dependent cell death in the descendants. Mouse embryos without centrioles are highly susceptible to this pathway and undergo embryonic arrest at mid-gestation. The complete loss of the centriolar core results in earlier and more severe phenotypes than that of other centrosomal proteins. Finally, different developing tissues possess varying thresholds and mount graded responses to the loss of centrioles that go beyond the germ layer of origin.
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