Journal of cell science最新文献_第10页

EdU tracking of leukocyte recruitment in mouse models of ischemic stroke and sterile lung inflammation. 缺血性脑卒中和无菌肺炎症小鼠模型白细胞募集的EdU跟踪。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-15 Epub Date: 2025-04-22 DOI: 10.1242/jcs.263835

Erika Arias, Maureen E Haynes, Neil A Nadkarni, Zoie K Lipfert, William A Muller, Ayush Batra, David P Sullivan

{"title":"EdU tracking of leukocyte recruitment in mouse models of ischemic stroke and sterile lung inflammation.","authors":"Erika Arias, Maureen E Haynes, Neil A Nadkarni, Zoie K Lipfert, William A Muller, Ayush Batra, David P Sullivan","doi":"10.1242/jcs.263835","DOIUrl":"10.1242/jcs.263835","url":null,"abstract":"The discovery of copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry) has significantly advanced the detection of proliferating cells by utilizing 5-ethynyl-2'-deoxyuridine (EdU). EdU, a thymidine analogue, is incorporated into DNA during replication and detected by the direct reaction with an azide-conjugated fluorophore. Traditionally, dividing cells are labeled using 5-bromodeoxyuridine (BrdU), another nucleotide analogue. However, BrdU detection is a harsh method that requires substantial sample processing, unlike EdU detection. EdU is classically used to identify proliferating cells; however, we report a streamlined methodology that uses EdU to label and track leukocyte recruitment that is compatible with flow cytometry and microscopy and preserves transgenic fluorophores. EdU labeling was performed in two different models of sterile inflammation: ischemic stroke and hydrochloric acid aspiration. EdU injection was timed to differentially label circulating monocytes, neutrophils and T cells. Tissue analysis showed EdU-positive monocytes and T cells were enriched in both inflammatory models. This suggests that recently divided monocytes and T cells are preferentially recruited to these vascular beds during inflammation and highlights the utility of this labeling approach to track leukocyte subtypes longitudinally during inflammation.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epithelial cell extrusion at a glance. 上皮细胞挤压一目了然。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-15 Epub Date: 2025-04-24 DOI: 10.1242/jcs.263786

Aline Grata, Romain Levayer

引用次数: 0

Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells. Med12与多种分化信号合作，促进胚胎干细胞有效的谱系转换。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-15 Epub Date: 2025-04-30 DOI: 10.1242/jcs.263794

Max Fernkorn, Christian Schröter

{"title":"Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells.","authors":"Max Fernkorn, Christian Schröter","doi":"10.1242/jcs.263794","DOIUrl":"10.1242/jcs.263794","url":null,"abstract":"Cell differentiation results from coordinated changes in gene transcription in response to combinations of signals. Fibroblast growth factor (FGF), Wnt and mammalian target of rapamycin (mTOR) signals regulate the differentiation of pluripotent mammalian cells towards embryonic and extraembryonic lineages, but how these signals cooperate with general transcriptional regulators is not fully resolved. Here, we report a genome-wide CRISPR screen that reveals both signaling components and general transcriptional regulators for differentiation-associated gene expression in mouse embryonic stem cells (mESCs). Focusing on the Mediator subunit-encoding Med12 gene as one of the strongest hits in the screen, we show that it regulates gene expression in parallel to FGF and mTOR signals. Loss of Med12 is compatible with differentiation along both the embryonic epiblast and the extraembryonic primitive endoderm lineage but impairs pluripotency gene expression and slows down transitions between pluripotency states. These findings suggest that Med12 helps pluripotent cells to efficiently execute transcriptional changes during differentiation, thereby modulating the effects of a broad range of signals.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In memoriam - Angelika A. Noegel. 纪念——安吉丽卡·a·诺格尔。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-15 Epub Date: 2025-04-25 DOI: 10.1242/jcs.264049

Annette Müller-Taubenberger, Ludwig Eichinger

引用次数: 0

Nanobodies against Cavin1 reveal structural flexibility and regulated interactions of its N-terminal coiled-coil domain. 抗Cavin1的纳米体揭示了其n端线圈结构域的结构灵活性和调节的相互作用。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-15 Epub Date: 2025-04-28 DOI: 10.1242/jcs.263756

Ya Gao, Vikas A Tillu, Yeping Wu, James Rae, Thomas E Hall, Kai-En Chen, Saroja Weeratunga, Qian Guo, Emma Livingstone, Wai-Hong Tham, Robert G Parton, Brett M Collins

{"title":"Nanobodies against Cavin1 reveal structural flexibility and regulated interactions of its N-terminal coiled-coil domain.","authors":"Ya Gao, Vikas A Tillu, Yeping Wu, James Rae, Thomas E Hall, Kai-En Chen, Saroja Weeratunga, Qian Guo, Emma Livingstone, Wai-Hong Tham, Robert G Parton, Brett M Collins","doi":"10.1242/jcs.263756","DOIUrl":"10.1242/jcs.263756","url":null,"abstract":"Caveolae are abundant plasma membrane structures that regulate signalling, membrane homeostasis and mechanoprotection. Their formation is driven by caveolins and cavins and their coordinated interactions with lipids. Here, we developed nanobodies against the trimeric HR1 coiled-coil domain of Cavin1. We identified specific nanobodies that do not perturb Cavin1 membrane binding and localise to caveolae when expressed in cells. The crystal structure of a nanobody-Cavin 1 HR1 complex reveals a symmetric 3:3 architecture as validated by mutagenesis. In this structure, the C-terminal half of the HR1 domain is disordered, suggesting that the nanobody stabilises an open conformation of Cavin1, which has previously been identified as important for membrane interactions. A phosphomimic mutation in a threonine-serine pair proximal to this region reveals selective regulation of Cavin2 and Cavin3 association. These studies provide new insights into cavin domains required for assembly of multiprotein caveolar assemblies and describe new nanobody tools for structural and functional studies of caveolae.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 8","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels. 压电致胰腺星状细胞的硬致性依赖于TRPC1和TRPV4通道。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-15 Epub Date: 2025-04-25 DOI: 10.1242/jcs.263846

Ilka Budde, André Schlichting, David Ing, Sandra Schimmelpfennig, Anna Kuntze, Benedikt Fels, Joelle M-J Romac, Sandip M Swain, Rodger A Liddle, Angela Stevens, Albrecht Schwab, Zoltán Pethő

{"title":"Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.","authors":"Ilka Budde, André Schlichting, David Ing, Sandra Schimmelpfennig, Anna Kuntze, Benedikt Fels, Joelle M-J Romac, Sandip M Swain, Rodger A Liddle, Angela Stevens, Albrecht Schwab, Zoltán Pethő","doi":"10.1242/jcs.263846","DOIUrl":"10.1242/jcs.263846","url":null,"abstract":"Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. However, the molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the contribution of the ion channels Piezo1, TRPC1 and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Our results demonstrate that optimal PSC durotaxis requires an intermediary level of ion channel activity, which we simulated via a numerically discretized mathematical model. These findings suggest that mechanosensitive Piezo1 channels detect the differential stiffness microenvironment. The resulting intracellular signals are amplified by TRPV4 and TRPC1 channels to guide efficient PSC durotaxis.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Compound screening in human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies. 在人气道基底细胞中进行复合筛选，确定Wnt通路激活剂作为潜在的促再生疗法。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-14 DOI: 10.1242/jcs.263487

Yuki Ishii, Jessica C Orr, Marie-Belle El Mdawar, Denise R Bairros de Pilger, David R Pearce, Kyren A Lazarus, Rebecca E Graham, Marko Z Nikolić, Robin Ketteler, Neil O Carragher, Sam M Janes, Robert E Hynds

{"title":"Compound screening in human airway basal cells identifies Wnt pathway activators as potential pro-regenerative therapies.","authors":"Yuki Ishii, Jessica C Orr, Marie-Belle El Mdawar, Denise R Bairros de Pilger, David R Pearce, Kyren A Lazarus, Rebecca E Graham, Marko Z Nikolić, Robin Ketteler, Neil O Carragher, Sam M Janes, Robert E Hynds","doi":"10.1242/jcs.263487","DOIUrl":"10.1242/jcs.263487","url":null,"abstract":"Regeneration of the airway epithelium restores barrier function and mucociliary clearance following lung injury and infection. The mechanisms regulating the proliferation and differentiation of tissue-resident airway basal stem cells remain incompletely understood. To identify compounds that promote human airway basal cell proliferation, we performed phenotype-based compound screening of 1429 compounds (from the ENZO and Prestwick Chemical libraries) in 384-well format using primary cells transduced with lentiviral luciferase. A total of 17 pro-proliferative compounds were validated in independent donor cell cultures, including the antiretroviral therapy agent abacavir and several Wnt signalling pathway-activating compounds. The effects of compounds on proliferation were further explored in colony formation and 3D organoid assays. Structurally and functionally related compounds that more potently induced Wnt pathway activation were investigated. One such compound, 1-azakenpaullone, induced Wnt target gene activation and basal cell proliferation in mice. Our results demonstrate the pro-proliferative effect of small-molecule Wnt pathway activators on airway basal cells. These findings contribute to the rationale to develop novel approaches to modulate Wnt signalling during airway epithelial repair.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Select autosomal dominant DFNA11 deafness variants activate Myo7A targeting in epithelial cells. 选择常染色体显性DFNA11耳聋突变激活Myo7A靶向上皮细胞。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-10 DOI: 10.1242/jcs.263982

Prashun Acharya, Garima Thapa, Xiayi Liao, Samaneh Matoo, Maura J Graves, Sarah Y Atallah, Ashna K Tipirneni, Tram Nguyen, Niki M Chhabra, Jaden Maschack, Mackenzie R Herod, Favour A Ohaezu, Alder Robison, Ashwini Mudaliyar, Jasvinder Bharaj, Nicole Roeser, Katherine Holmes, Vishwaas Nayak, Rayah Alsayed, Benjamin J Perrin, Scott W Crawley

{"title":"Select autosomal dominant DFNA11 deafness variants activate Myo7A targeting in epithelial cells.","authors":"Prashun Acharya, Garima Thapa, Xiayi Liao, Samaneh Matoo, Maura J Graves, Sarah Y Atallah, Ashna K Tipirneni, Tram Nguyen, Niki M Chhabra, Jaden Maschack, Mackenzie R Herod, Favour A Ohaezu, Alder Robison, Ashwini Mudaliyar, Jasvinder Bharaj, Nicole Roeser, Katherine Holmes, Vishwaas Nayak, Rayah Alsayed, Benjamin J Perrin, Scott W Crawley","doi":"10.1242/jcs.263982","DOIUrl":"10.1242/jcs.263982","url":null,"abstract":"Myosin-7A (Myo7A) is a motor protein crucial for the organization and function of stereocilia, specialized actin-rich protrusions on the surface of inner ear hair cells that mediate hearing. Variants in Myo7A cause several forms of genetic hearing loss, including autosomal dominant DFNA11 deafness. Despite its importance, the structural elements that control Myo7A within cells are not well understood. In this study, we used cultured kidney epithelial cells to screen for mutations that activate the motor-dependent targeting of Myo7A to the tips of apical microvilli on these cells. Our findings reveal that the targeting of Myo7A is regulated by specific IQ motifs within its lever arm and that this regulation can function at least partially independent of its tail sequence. Importantly, we demonstrate that many of the DFNA11 deafness variants reported in patients activate Myo7A targeting, providing a potential explanation for the autosomal dominant genetics of this form of deafness.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ATG9A vesicles are a subtype of intracellular nanovesicle. ATG9A囊泡是细胞内纳米囊泡的一个亚型。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-09 DOI: 10.1242/jcs.263852

Mary Fesenko, Daniel J Moore, Peyton Ewbank, Elizabeth Courthold, Stephen J Royle

引用次数: 0

Announcing the JCS-David Stephens Prize and the 2024 winner Anja Konietzny. 宣布JCS-David Stephens奖和2024年获奖者Anja Konietzny。

IF 3.3 3区生物学

Journal of cell science Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI: 10.1242/jcs.263973

Michael Way

引用次数: 0