Developmental cell最新文献

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The ups and downs of maturing zonated hepatoctyes 成熟分带性肝细胞的起起落落

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-11 DOI: 10.1016/j.devcel.2026.02.009

Tabea L. Stephan, Pamela A. Hoodless

Current in vitro protocols differentiating hepatocytes fail to activate mature metabolic genes, induce zone-specific phenotypes, and suppress fetal liver signatures. In this issue, Taguchi, Magalhães et al.¹ used CRISPR-Cas9 screening in a mouse model of hepatic development to identify Nr1i3 and Nfix as regulators of hepatocyte maturation and zonation.

目前的体外方案分化肝细胞不能激活成熟的代谢基因，诱导区域特异性表型，并抑制胎儿肝脏特征。在这一期中，Taguchi, magalh等人1在小鼠肝脏发育模型中使用CRISPR-Cas9筛选，鉴定出Nr1i3和Nfix是肝细胞成熟和分区的调节因子。

引用次数: 0

Gut check: Peroxisomes as a missing link in long COVID intestinal repair 肠道检查：过氧化物酶体是长期COVID肠道修复的缺失环节

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-11 DOI: 10.1016/j.devcel.2026.02.011

Karen He, Andrew James Simmonds

Long COVID is often associated with persistent gastrointestinal dysfunction. In this issue of Developmental Cell, Wang et al. reveal that intestinal SARS-CoV-2 reservoirs disrupt VLCFA-mediated peroxisome signaling needed for epithelial repair. Patient studies, combined with Drosophila and mammalian models, identify an underlying mechanism and FDA-approved peroxisome activators as potential therapeutics.

长冠状病毒通常与持续的胃肠道功能障碍有关。在这一期的Developmental Cell中，Wang等人揭示了肠道SARS-CoV-2储存库破坏了上皮修复所需的vlcfa介导的过氧化物酶体信号。结合果蝇和哺乳动物模型的患者研究，确定了潜在的机制和fda批准的过氧化物酶体激活剂作为潜在的治疗方法。

引用次数: 0

Nitrogen regulates flowering through FKF1 condensate dynamics 氮通过FKF1凝析物动力学调节开花

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-11 DOI: 10.1016/j.devcel.2026.02.001

Huikyong Cho, Chanakan Prom-u-thai, Hatem Rouached

Plant flowering integrates environmental and nutrient cues, yet how mineral nutrients interface with core flowering pathways remains unclear. In this issue of Developmental Cell, Lyu et al. identify a nitrogen-responsive module in which nitrogen availability alters FKF1 physical organization and protein interactions, thereby regulating FT4 stability and controlling flowering time.

植物开花综合了环境和营养因素，但矿物营养如何与核心开花途径相结合仍不清楚。在本期的Developmental Cell中，Lyu等人发现了一个氮响应模块，其中氮的可用性改变了FKF1的物理组织和蛋白质相互作用，从而调节FT4的稳定性和控制开花时间。

引用次数: 0

MYRF restrains mesothelial plasticity to protect the lung MYRF抑制间皮可塑性以保护肺

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-11 DOI: 10.1016/j.devcel.2026.02.008

Rachel Warren, Stijn De Langhe

In this issue of Developmental Cell, Luna et al.¹ identify myelin regulatory factor (MYRF) as a critical determinant of lung mesothelial specification and quiescence. Their study demonstrates that MYRF loss leads to congenital diaphragmatic hernia or a pleuroparenchymal fibroelastosis-like phenotype, revealing the mesothelium as an actively restrained progenitor population.

在本期《发育细胞》中，Luna等人1发现髓鞘调节因子（MYRF）是肺间皮分化和静止的关键决定因素。他们的研究表明，MYRF缺失导致先天性膈疝或胸膜实质纤维弹性变样表型，揭示了间皮细胞是一个受到积极抑制的祖细胞群。

引用次数: 0

BAF60C links nucleolar stress to β cell dysfunction in type 2 diabetes through controlling Reg3b mRNA decay BAF60C通过控制Reg3b mRNA衰变将核仁应激与2型糖尿病β细胞功能障碍联系起来

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-09 DOI: 10.1016/j.devcel.2026.02.006

Zhuoying Yang, Shuaishuai Zhu, Cheng-An Lyu, Hongxing Fu, Wei Chen, Xinyuan Qiu, Wenjing Zhang, Ting Yu, Miqi Yang, Zhe Yu Zhang, Qiyao Xu, Xiao Z. Shen, Peter van Endert, Sheng Yan, Zhuo-Xian Meng

The islet immune microenvironment contributes critically to β cell dysfunction in type 2 diabetes (T2D), but its regulatory mechanisms remain unclear. We show that β cell dysfunction in T2D patients and diabetic mice correlates with elevated nucleolar stress and reduced expression of BAF60C, a switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling factor. β cell-specific BAF60C deletion aggravates high-fat diet (HFD)-induced hyperglycemia, nucleolar stress, and islet inflammation, whereas BAF60C overexpression displays protection. BAF60C suppresses islet inflammation by promoting REG3B expression and secretion, thereby modulating β cell-macrophage crosstalk. Mechanistically, BAF60C forms an RNA-protein complex with nucleophosmin (NPM1) and Reg3b mRNA to modulate Reg3b mRNA decay. Restoration of the BAF60C-REG3B axis through REG3B supplementation or exercise alleviates inflammation and improves glucose homeostasis in obese and T2D mice, revealing a non-canonical role for BAF60C in linking nucleolar stress to β cell failure.

胰岛免疫微环境对2型糖尿病（T2D）患者的β细胞功能障碍起着至关重要的作用，但其调节机制尚不清楚。我们发现t2dm患者和糖尿病小鼠的β细胞功能障碍与核核应激升高和BAF60C（一种开关缺陷/蔗糖不发酵（SWI/SNF）染色质重塑因子）表达降低相关。β细胞特异性BAF60C缺失会加重高脂肪饮食（HFD）诱导的高血糖、核仁应激和胰岛炎症，而BAF60C过表达则具有保护作用。BAF60C通过促进REG3B的表达和分泌来抑制胰岛炎症，从而调节β -巨噬细胞串扰。机制上，BAF60C与核磷蛋白（NPM1）和Reg3b mRNA形成rna -蛋白复合物，调节Reg3b mRNA的衰变。通过补充REG3B或运动来恢复BAF60C-REG3B轴可以减轻肥胖和T2D小鼠的炎症并改善葡萄糖稳态，揭示了BAF60C在核核应激与β细胞衰竭之间的非规范作用。

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引用次数: 0

An H3K4me3 reader recruits the positive transcription elongation factor B complex to facilitate transcription elongation in Arabidopsis 在拟南芥中，H3K4me3读取器募集正转录延伸因子B复合体以促进转录延伸

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-04 DOI: 10.1016/j.devcel.2026.02.005

Xiaodan Yu, Xuerui Lu, Chong Huang, Zhiping Deng, Songge Chai, Jiamu Du, Ziqian Yang, Xueao Zheng, Lili Wang, Shunping Yan

Transcription by RNA polymerase II (RNA Pol II) is a tightly regulated process in eukaryotes. A recent study revealed that the trimethylation of histone H3 at lysine 4 (H3K4me3) activates gene expression by promoting RNA Pol II pause-release and transcription elongation rather than transcription initiation. However, the molecular mechanisms linking H3K4me3 to transcription elongation remain largely unclear. Here, we show that an H3K4me3 reader regulates this process. A genetic screening in Arabidopsis reveals that root growth in salicylic acid 1 (RGSA1) is required for the transcription of genes induced by the plant hormone salicylic acid. RGSA1 contains a cysteine-tryptophan domain, which is essential for its binding to H3K4me3. RGSA1 mainly occupies transcription start sites, where it recruits the positive transcription elongation factor B (P-TEFb) complex to facilitate transcription elongation. Given the evolutionary conservation of H3K4me3 readers and P-TEFb, our findings may represent a conserved mechanism underlying transcription elongation across eukaryotes.

RNA聚合酶II （RNA Pol II）转录是真核生物中一个受到严格调控的过程。最近的一项研究表明，组蛋白H3在赖氨酸4位点的三甲基化（H3K4me3）通过促进RNA Pol II暂停释放和转录延长而不是转录起始来激活基因表达。然而，H3K4me3与转录延伸的分子机制仍不清楚。在这里，我们展示了H3K4me3阅读器调节这一过程。在拟南芥中进行的遗传筛选表明，水杨酸1基因（RGSA1）的根生长是植物激素水杨酸诱导基因转录所必需的。RGSA1含有一个半胱氨酸-色氨酸结构域，这是它与H3K4me3结合所必需的。RGSA1主要占据转录起始位点，在此招募转录延伸因子B （P-TEFb）复合体促进转录延伸。考虑到H3K4me3读取器和P-TEFb的进化保守性，我们的发现可能代表了真核生物转录延伸的保守机制。

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引用次数: 0

Multiscale mechanisms driving tissue rupture by invading cells 入侵细胞驱动组织破裂的多尺度机制

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-04 DOI: 10.1016/j.devcel.2026.01.016

Selwin K. Wu, Fuqiang Sun, Celestine Z. Ho, Yuting Lou, Christina Bao-Xian Huang, Mui Hoon Nai, Jingwei Xiao, Murat Shagirov, Jasmine Fei Li Chin, Diana Lim, Suzie Verma, David S.P. Tan, Philippe Marcq, Alpha S. Yap, Chwee Teck Lim, Tetsuya Hiraiwa, Yuan Lin, Boon Chuan Low

Cells migrate and invade tissues during development, immune responses, and cancer. Collective invasion is generally understood to be driven by invading cells unjamming and pushing through barriers such as the extracellular matrix and surrounding tissues. Whether these barriers actively contribute to invasion remains unclear. Using ovarian adenocarcinoma spheroids invading mesothelium derived from benign pleural effusions as an experimental model, combined with modeling, we examine invasion across molecular to multicellular scales. We identify intercellular integrin adhesions linking invasive leader cells to the tissue barrier, triggering apical constrictions within the barrier. This constriction shrinks cell-cell contacts, leading to barrier rupture. Thus, the tissue barrier plays a mechanically active role in invasion. Rather than cells pushing through, we find that coordinated subcellular contractility between the invading leader cell and the barrier drives barrier tensile rupture and invasion, independent of a jamming transition. Together, our findings challenge prevailing paradigms of collective cell invasion.

细胞在发育、免疫反应和癌症过程中迁移和侵入组织。集体侵袭通常被认为是由入侵细胞解除干扰和推动屏障，如细胞外基质和周围组织。这些障碍是否会积极促进入侵尚不清楚。利用良性胸腔积液中卵巢腺癌球体侵入间皮作为实验模型，结合建模，我们研究了从分子到多细胞尺度的侵袭。我们发现细胞间整合素粘附将侵入性领导细胞连接到组织屏障，触发屏障内的顶端收缩。这种收缩收缩了细胞间的接触，导致屏障破裂。因此，组织屏障在入侵中起着机械的积极作用。我们发现，入侵的领导细胞和屏障之间的协调的亚细胞收缩性驱动屏障的拉伸破裂和入侵，而不是细胞推进，独立于干扰过渡。总之，我们的发现挑战了集体细胞入侵的主流范式。

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引用次数: 0

Hematopoietic stem cells activate a latent differentiation pathway to facilitate recovery after 5-fluorouracil-induced myeloablation. 造血干细胞激活潜在分化途径，促进5-氟尿嘧啶诱导骨髓消融后的恢复。

IF 8.7 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-02 DOI: 10.1016/j.devcel.2026.02.003

Zhen Zhang, Ben Jin, Chenyu You, Ya Li, Li Lin, Jianlong Sun

Myeloablative chemotherapy induces hematopoietic regeneration, a process orchestrated by hematopoietic stem cells (HSCs). Although prior studies have documented enhanced HSC differentiation during this process, the temporal changes in HSC fate in response to such stress remain unclear. Here, we employed lineage tracing and mathematical modeling to investigate the cell-fate dynamics of Endothelial Protein C Receptor (EPCR)-high HSCs following 5-fluorouracil (5-FU)-induced myeloablation. Our analysis revealed a transient surge in HSC differentiation immediately after 5-FU treatment, generating primarily myeloid-biased multipotent progenitors (MPPs)-subsets that typically receive limited HSC input under steady-state conditions. Following this initial cell-fate switch, elevated HSC differentiation persisted but rapidly reverted to the homeostatic differentiation pattern observed in unperturbed hematopoiesis. Additionally, our data highlight a substantial contribution of MPPs to myeloid and lymphoid lineage regeneration following 5-FU challenge. Together, these findings delineate the sequential fate transitions adopted by HSCs during severe myeloablation and identify stage-specific differentiation patterns of HSCs in stress hematopoiesis.

骨髓清除化疗诱导造血再生，这是一个由造血干细胞（hsc）协调的过程。尽管先前的研究已经证实在这一过程中增强了HSC分化，但HSC命运在这种应激反应中的时间变化尚不清楚。在这里，我们采用谱系追踪和数学模型来研究内皮蛋白C受体（EPCR）高造血干细胞在5-氟尿嘧啶（5-FU）诱导骨髓消融后的细胞命运动态。我们的分析显示，在5-FU治疗后，HSC分化立即出现短暂的激增，主要产生骨髓偏向性多能祖细胞（mpp），这些亚群通常在稳态条件下接受有限的HSC输入。在这种初始的细胞命运转换之后，升高的HSC分化持续存在，但迅速恢复到在未受干扰的造血中观察到的稳态分化模式。此外，我们的数据强调了mpp对5-FU挑战后髓系和淋巴系再生的重大贡献。总之，这些发现描述了造血干细胞在严重骨髓消融过程中所采用的顺序命运转变，并确定了应激造血中造血干细胞的阶段特异性分化模式。

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引用次数: 0

A plant histone H3.3-specific amino acid safeguards the deposition of H3K36 methylation for proper development and stress responses. 植物组蛋白h3.3特异性氨基酸保护H3K36甲基化沉积，以促进正常发育和应激反应。

IF 8.7 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-02 DOI: 10.1016/j.devcel.2026.02.002

Xiaoyi Li, Huairen Zhang, Lijun Ma, Mande Xue, Qian Liu, Zdravko J Lorković, Frédéric Berger, Danhua Jiang

Histone variants are key regulators of chromatin function. The H3 variants H3.1 and H3.3 evolved independently in animals and plants and differ at amino acid position 31, where H3.1 contains alanine (A), whereas H3.3 carries serine (S) in animals or threonine (T) in plants. Although S and T can both be phosphorylated, the biological significance of plants having selectively adopted T over S remains unclear. Here, we report that H3.3T31 plays a critical role in plant development and stress responses by promoting H3K36me3 on H3.3. T31 prevents plant-specific H3K27 methyltransferases ATXR5 and ATXR6 from depositing H3K27me1, which otherwise inhibits the H3K36 methyltransferase EFS. The substitution of H3.3T31 with S or A increases ATXR5/6 activity and elevates H3K27me1, leading to reduced H3K36me3. Together, these findings suggest co-selection of the plant-specific H3.3T31 residue and ATXR5/6 to ensure the preferential accumulation of H3K27me1 on H3.1 and H3K36me3 on H3.3, thereby supporting chromatin function in plants.

组蛋白变异是染色质功能的关键调节因子。H3变体H3.1和H3.3在动物和植物中独立进化，在氨基酸位置31处不同，其中H3.1含有丙氨酸(A)，而H3.3在动物中携带丝氨酸(S)，在植物中携带苏氨酸(T)。虽然S和T都可以被磷酸化，但植物选择性地接受T而不是S的生物学意义尚不清楚。在这里，我们报道了H3.3 t31通过促进H3.3上的H3K36me3在植物发育和胁迫响应中发挥关键作用。T31阻止植物特异性H3K27甲基转移酶ATXR5和ATXR6沉积H3K27me1，否则会抑制H3K36甲基转移酶EFS。用S或A取代H3.3T31会增加ATXR5/6活性，升高H3K27me1，导致H3K36me3降低。综上所述，这些发现表明植物特异性H3.3 t31残基和ATXR5/6的共同选择确保了H3K27me1在H3.1和H3K36me3在H3.3上的优先积累，从而支持了植物的染色质功能。

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引用次数: 0

Nuclear phosphoinositide signaling in cell biology and disease 核磷酸肌肽信号在细胞生物学和疾病中的应用

IF 11.8 1区生物学 Q1 CELL BIOLOGY

Developmental cell

Pub Date : 2026-03-02 DOI: 10.1016/j.devcel.2026.02.004

Yanan Sun, Fengting Liu, Chunbo Chen, Jichao Sun, Mo Chen

Phosphatidylinositol phosphates (PIPs), or phosphoinositides, are minor yet essential phospholipids that govern diverse cellular processes, from membrane trafficking to signal transduction. While traditionally studied within the cell membranes, emerging evidence reveals their dynamic metabolism and critical functions in the nucleus, particularly within the non-membrane nucleoplasm, continually reshaping our understanding of the nuclear PIP-lipidome and its therapeutic potential. However, an updated overview of the nuclear PIP landscape and its selective modulators remains lacking. This review addresses this gap by providing an integrated summary of nuclear PIP signaling components, encompassing their structures, species, distribution, transport, and metabolic regulation. A focus is placed on pharmacological modulation, including inhibitors and activators targeting nuclear phosphatidylinositol (PI/PtdIns) transfer proteins and PIP-metabolizing enzymes, with attention to structure-based inhibitor classes and representative clinical-stage compounds. We conclude by outlining therapeutic opportunities that arise from targeting the nuclear PIP pathway, particularly in the context of cancer, cardiovascular disease, and neurodegeneration.

磷脂酰肌醇磷酸（PIPs）或磷酸肌苷是一种次要但必需的磷脂，它控制着从膜运输到信号转导等多种细胞过程。虽然传统上是在细胞膜内进行研究，但新出现的证据揭示了它们在细胞核中的动态代谢和关键功能，特别是在非膜核质中，不断重塑我们对核pip -脂质组及其治疗潜力的理解。然而，核PIP景观及其选择性调节剂的最新概述仍然缺乏。这篇综述通过提供核PIP信号成分的综合总结，包括它们的结构、种类、分布、运输和代谢调节，解决了这一空白。重点放在药理学调节上，包括针对核磷脂酰肌醇（PI/PtdIns）转移蛋白和pip代谢酶的抑制剂和激活剂，并关注基于结构的抑制剂类别和具有代表性的临床阶段化合物。最后，我们概述了针对核PIP通路的治疗机会，特别是在癌症、心血管疾病和神经退行性疾病的背景下。

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