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Therapeutic application of extracellular vesicular EGFR isoform D as a co-drug to target squamous cell cancers with tyrosine kinase inhibitors 将细胞外囊泡表皮生长因子受体同工酶 D 作为辅助药物用于鳞状细胞癌酪氨酸激酶抑制剂的治疗应用
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-31 DOI: 10.1016/j.devcel.2024.07.003
{"title":"Therapeutic application of extracellular vesicular EGFR isoform D as a co-drug to target squamous cell cancers with tyrosine kinase inhibitors","authors":"","doi":"10.1016/j.devcel.2024.07.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.003","url":null,"abstract":"<p>Targeting wild-type epidermal growth factor receptor (EGFR) using tyrosine kinase inhibitors (TKIs) never achieved its purported success in cancers such as head and neck squamous cell carcinoma, which are largely EGFR-dependent. We had previously shown that exceptional responders to TKIs have a genetic aberration that results in overexpression of an EGFR splice variant, isoform D (IsoD). IsoD lacks an integral transmembrane and kinase domain and is secreted in extracellular vesicles (EVs) in TKI-sensitive patient-derived cultures. Remarkably, the exquisite sensitivity to TKIs could be transferred to TKI-resistant tumor cells, and IsoD protein in the EV is necessary and sufficient to transfer the phenotype <em>in vitro</em> and <em>in vivo</em> across multiple models and drugs. This drug response requires an intact endocytic mechanism, binding to full-length EGFR, and signaling through Src-phosphorylation within the endosomal compartment. We propose a therapeutic strategy using EVs containing EGFR IsoD as a co-drug to expand the use of TKI therapy to EGFR-driven cancers.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"34 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The rice E3 ubiquitin ligase-transcription factor module targets two trypsin inhibitors to enhance broad-spectrum disease resistance 水稻 E3 泛素连接酶-转录因子模块以两种胰蛋白酶抑制剂为靶标，增强广谱抗病性
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-31 DOI: 10.1016/j.devcel.2024.07.019
{"title":"The rice E3 ubiquitin ligase-transcription factor module targets two trypsin inhibitors to enhance broad-spectrum disease resistance","authors":"","doi":"10.1016/j.devcel.2024.07.019","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.019","url":null,"abstract":"No Abstract","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"74 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Soybean symbiotic-nodule zonation and cell differentiation are defined by NIN2 signaling and GH3-dependent auxin homeostasis 大豆的共生结节分带和细胞分化由 NIN2 信号和 GH3 依赖性辅助素平衡决定
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-24 DOI: 10.1016/j.devcel.2024.07.001
{"title":"Soybean symbiotic-nodule zonation and cell differentiation are defined by NIN2 signaling and GH3-dependent auxin homeostasis","authors":"","doi":"10.1016/j.devcel.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.001","url":null,"abstract":"<p>Symbiotic nodules comprise two classes, indeterminate and determinate, defined by the presence/absence of apical meristem and developmental zonation. Why meristem and zonation are absent from determinate nodules remains unclear. Here, we define cell types in developing soybean nodules, highlighting the undifferentiated infection zones and differentiated nitrogen-fixation zones. Auxin governs infection zone maintenance. GRETCHEN HAGEN 3 (GH3) enzymes deactivate auxin by conjugation and promote cell differentiation. <em>gh3</em> mutants increased undifferentiated cells and enlarged infection zones. The central symbiosis-transcription factor NIN2a activates <em>GH3.1</em> to reduce auxin levels and facilitates cell differentiation. High auxin promotes NIN2a protein accumulation and enhances signaling, further deactivating auxin and depleting infection zones. Our findings shed light on the NIN2a-GH3-auxin module that drives soybean nodule cell differentiation. This study challenges our understanding of determinate nodule development and proposes that the regulation of nodule zonation offers valuable insights into broader mechanisms of cell differentiation across plant species.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"24 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arabidopsis COP1 suppresses root hair development by targeting type I ACS proteins for ubiquitination and degradation 拟南芥 COP1 通过靶向 I 型 ACS 蛋白进行泛素化和降解来抑制根毛发育
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-24 DOI: 10.1016/j.devcel.2024.06.021
{"title":"Arabidopsis COP1 suppresses root hair development by targeting type I ACS proteins for ubiquitination and degradation","authors":"","doi":"10.1016/j.devcel.2024.06.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.021","url":null,"abstract":"<p>Root hairs (RHs) are an innovation of vascular plants whose development is coordinated by endogenous and environmental cues, such as ethylene and light conditions. However, the potential crosstalk between ethylene and light conditions in RH development is unclear. We report that <em>Arabidopsis</em> constitutive photomorphogenic 1 (COP1) integrates ethylene and light signaling to mediate RH development. Darkness suppresses RH development largely through <em>COP1</em>. COP1 inhibits both cell fate determination of trichoblast and tip growth of RHs based on pharmacological, genetic, and physiological analyses. Indeed, COP1 interacts with and catalyzes the ubiquitination of ACS2 and ACS6. COP1- or darkness-promoted proteasome-dependent degradation of ACS2/6 leads to a low ethylene level in underground tissues. The negative role of COP1 in RH development by downregulating ethylene signaling may be coordinated with the positive role of COP1 in hypocotyl elongation by upregulating ethylene signaling, providing an evolutionary advantage for seedling fitness.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"22 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autocrine glutamate signaling drives cell competition in Drosophila 谷氨酸自分泌信号驱动果蝇的细胞竞争
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-23 DOI: 10.1016/j.devcel.2024.06.022
{"title":"Autocrine glutamate signaling drives cell competition in Drosophila","authors":"","doi":"10.1016/j.devcel.2024.06.022","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.022","url":null,"abstract":"<p>Cell competition is an evolutionarily conserved quality control process that eliminates suboptimal or potentially dangerous cells. Although differential metabolic states act as direct drivers of competition, how these are measured across tissues is not understood. Here, we demonstrate that vesicular glutamate transporter (VGlut) and autocrine glutamate signaling are required for cell competition and <em>Myc</em>-driven super-competition in the <em>Drosophila</em> epithelia. We find that the loss of glutamate-stimulated VGlut&gt;NMDAR&gt;CaMKII&gt;CrebB signaling triggers loser status and cell death under competitive settings via the autocrine induction of TNF. This in turn drives TNFR&gt;JNK activation, triggering loser cell elimination and PDK/LDH-dependent metabolic reprogramming. Inhibiting caspases or preventing loser cells from transferring lactate to their neighbors nullifies cell competition. Further, in a <em>Drosophila</em> model for premalignancy, <em>Myc</em>-overexpressing clones co-opt this signaling circuit to acquire super-competitor status. Targeting glutamate signaling converts <em>Myc</em> “super-competitor” clones into “losers,” highlighting new therapeutic opportunities to restrict the evolution of fitter clones.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"48 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rigidity percolation and active advection synergize in the actomyosin cortex to drive amoeboid cell motility 肌动蛋白皮层中的刚性渗流和主动平流协同驱动变形虫细胞运动
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-23 DOI: 10.1016/j.devcel.2024.06.023
{"title":"Rigidity percolation and active advection synergize in the actomyosin cortex to drive amoeboid cell motility","authors":"","doi":"10.1016/j.devcel.2024.06.023","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.023","url":null,"abstract":"<p>Spontaneous locomotion is a common feature of most metazoan cells, generally attributed to the properties of actomyosin networks. This force-producing machinery has been studied down to the most minute molecular details, especially in lamellipodium-driven migration. Nevertheless, how actomyosin networks work inside contraction-driven amoeboid cells still lacks unifying principles. Here, using stable motile blebs from HeLa cells as a model amoeboid motile system, we imaged the dynamics of the actin cortex at the single filament level and revealed the co-existence of three distinct rheological phases. We introduce “advected percolation,” a process where rigidity percolation and active advection synergize, spatially organizing the actin network’s mechanical properties into a minimal and generic locomotion mechanism. Expanding from our observations on simplified systems, we speculate that this model could explain, down to the single actin filament level, how amoeboid cells, such as cancer or immune cells, can propel efficiently through complex 3D environments.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"65 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Very long-chain fatty acids control peroxisome dynamics via a feedback loop in intestinal stem cells during gut regeneration 肠道再生过程中，极长链脂肪酸通过肠道干细胞的反馈回路控制过氧物酶体动力学
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-23 DOI: 10.1016/j.devcel.2024.06.020
{"title":"Very long-chain fatty acids control peroxisome dynamics via a feedback loop in intestinal stem cells during gut regeneration","authors":"","doi":"10.1016/j.devcel.2024.06.020","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.020","url":null,"abstract":"<p>Peroxisome dynamics are crucial for intestinal stem cell (ISC) differentiation and gut regeneration. However, the precise mechanisms that govern peroxisome dynamics within ISCs during gut regeneration remain unknown. Using mouse colitis and <em>Drosophila</em> intestine models, we have identified a negative-feedback control mechanism involving the transcription factors peroxisome proliferator-activated receptors (PPARs) and SOX21. This feedback mechanism effectively regulates peroxisome abundance during gut regeneration. Following gut injury, the released free very long-chain fatty acids (VLCFAs) increase peroxisome abundance by stimulating PPARs-PEX11s signaling. PPARs act to stimulate peroxisome fission and inhibit pexophagy. SOX21, which acts downstream of peroxisomes during ISC differentiation, induces peroxisome elimination through pexophagy while repressing PPAR expression. Hence, PPARs and SOX21 constitute a finely tuned negative-feedback loop that regulates peroxisome dynamics. These findings shed light on the complex molecular mechanisms underlying peroxisome regulation in ISCs, contributing to our understanding of gut renewal and repair.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"50 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Factors governing cellular reprogramming competence in Arabidopsis adventitious root formation 拟南芥不定根形成过程中影响细胞重编程能力的因素
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-22 DOI: 10.1016/j.devcel.2024.06.019
{"title":"Factors governing cellular reprogramming competence in Arabidopsis adventitious root formation","authors":"","doi":"10.1016/j.devcel.2024.06.019","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.019","url":null,"abstract":"<p>Developmental reprogramming allows for flexibility in growth and adaptation to changing environmental conditions. In plants, wounding events can result in new stem cell niches and lateral organs. Adventitious roots develop from aerial parts of the plant and are regulated by multiple stimuli, including wounding. Here, we find that <em>Arabidopsis thaliana</em> seedlings wounded at the hypocotyl-root junction reprogram certain pericycle cells to produce adventitious roots proximal to the wound site. We have determined that competence for this reprogramming is controlled; basal cells close to the wound site can produce adventitious roots, whereas cells distal from the wound site mostly cannot. We found that altering cytokinin response or indole-3-butyric acid (IBA)-to-(indole-3-acetic acid) IAA conversion resulted in an expanded adventitious root competence zone and delineated the connection between these pathways. Our work highlights the importance of endogenous IBA-derived auxin and its interaction with cytokinin in adventitious root formation and the regenerative properties of plants.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"65 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TDRD1 phase separation drives intermitochondrial cement assembly to promote piRNA biogenesis and fertility TDRD1 相分离驱动半软骨间胶结物组装，促进 piRNA 的生物生成和生育能力
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-18 DOI: 10.1016/j.devcel.2024.06.017
{"title":"TDRD1 phase separation drives intermitochondrial cement assembly to promote piRNA biogenesis and fertility","authors":"","doi":"10.1016/j.devcel.2024.06.017","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.017","url":null,"abstract":"<p>The intermitochondrial cement (IMC) is a prominent germ granule that locates among clustered mitochondria in mammalian germ cells. Serving as a key platform for Piwi-interacting RNA (piRNA) biogenesis; however, how the IMC assembles among mitochondria remains elusive. Here, we identify that Tudor domain-containing 1 (TDRD1) triggers IMC assembly via phase separation. TDRD1 phase separation is driven by the cooperation of its tetramerized coiled-coil domain and dimethylarginine-binding Tudor domains but is independent of its intrinsically disordered region. TDRD1 is recruited to mitochondria by MILI and sequentially enhances mitochondrial clustering and triggers IMC assembly via phase separation to promote piRNA processing. TDRD1 phase separation deficiency in mice disrupts IMC assembly and piRNA biogenesis, leading to transposon de-repression and spermatogenic arrest. Moreover, TDRD1 phase separation is conserved in vertebrates but not in invertebrates. Collectively, our findings demonstrate a role of phase separation in germ granule formation and establish a link between membrane-bound organelles and membrane-less organelles.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"26 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2 小鼠脊髓损伤时空分子图谱确定了一个独特的星形胶质细胞亚群和 IGFBP2 的治疗潜力
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-07-18 DOI: 10.1016/j.devcel.2024.06.016
{"title":"A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2","authors":"","doi":"10.1016/j.devcel.2024.06.016","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.06.016","url":null,"abstract":"<p>Spinal cord injury (SCI) triggers a cascade of intricate molecular and cellular changes that determine the outcome. In this study, we resolve the spatiotemporal organization of the injured mouse spinal cord and quantitatively assess <em>in situ</em> cell-cell communication following SCI. By analyzing existing single-cell RNA sequencing datasets alongside our spatial data, we delineate a subpopulation of <em>Igfbp2</em>-expressing astrocytes that migrate from the white matter (WM) to gray matter (GM) and become reactive upon SCI, termed Astro-GMii. Further, <em>Igfbp2</em> upregulation promotes astrocyte migration, proliferation, and reactivity, and the secreted IGFBP2 protein fosters neurite outgrowth. Finally, we show that IGFBP2 significantly reduces neuronal loss and remarkably improves the functional recovery in a mouse model of SCI <em>in vivo</em>. Together, this study not only provides a comprehensive molecular atlas of SCI but also exemplifies how this rich resource can be applied to endow cells and genes with functional insight and therapeutic potential.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"35 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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