{"title":"Chromatin-site-specific accessibility: A microtopography-regulated door into the stem cell fate.","authors":"Wenyan Zhou, Junxin Lin, Qianchun Wang, Xianliu Wang, Xudong Yao, Yiyang Yan, Wei Sun, Qiuwen Zhu, Xiaoan Zhang, Xiaozhao Wang, Baohua Ji, Hongwei Ouyang","doi":"10.1016/j.celrep.2024.115106","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115106","url":null,"abstract":"<p><p>Biomaterials that mimic extracellular matrix topography are crucial in tissue engineering. Previous research indicates that certain biomimetic topography can guide stem cells toward multiple specific lineages. However, the mechanisms by which topographic cues direct stem cell differentiation remain unclear. Here, we demonstrate that microtopography influences nuclear tension in mesenchymal stem cells (MSCs), shaping chromatin accessibility and determining lineage commitment. On aligned substrates, MSCs exhibit high cytoskeletal tension along the fiber direction, creating anisotropic nuclear stress that opens chromatin sites for neurogenic, myogenic, and tenogenic genes via transcription factors like Nuclear receptor TLX (TLX). In contrast, random substrates induce isotropic nuclear stress, promoting chromatin accessibility for osteogenic and chondrogenic genes through Runt-related transcription factors (RUNX). Our findings reveal that aligned and random microtopographies direct site-specific chromatin stretch and lineage-specific gene expression, priming MSCs for distinct lineages. This study introduces a novel framework for understanding how topographic cues govern cell fate in tissue repair and regeneration.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115106"},"PeriodicalIF":7.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892527","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}
Cell reportsPub Date : 2024-12-25DOI: 10.1016/j.celrep.2024.115111
Kevin C Osum, Samuel H Becker, Peter D Krueger, Jason S Mitchell, Sung-Wook Hong, Ian R Magill, Marc K Jenkins
{"title":"A minority of Th1 and Tfh effector cells express survival genes shared by memory cell progeny that require IL-7 or TCR signaling to persist.","authors":"Kevin C Osum, Samuel H Becker, Peter D Krueger, Jason S Mitchell, Sung-Wook Hong, Ian R Magill, Marc K Jenkins","doi":"10.1016/j.celrep.2024.115111","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.115111","url":null,"abstract":"<p><p>It is not clear how CD4<sup>+</sup> memory T cells are formed from a much larger pool of earlier effector cells. We found that transient systemic bacterial infection rapidly generates several antigen-specific T helper (Th)1 and T follicular helper (Tfh) cell populations with different tissue residence behaviors. Although most cells of all varieties had transcriptomes indicative of cell stress and death at the peak of the response, some had already acquired a memory cell signature characterized by expression of genes involved in cell survival. Each Th1 and Tfh cell type was maintained long term by interleukin (IL)-7, except germinal center Tfh cells, which depended on a T cell antigen receptor (TCR) signal. The results indicate that acute infection induces rapid differentiation of Th1 and Tfh cells, a minority of which quickly adopt the gene expression profile of memory cells and survive by signals from the IL-7 receptor or TCR.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 1","pages":"115111"},"PeriodicalIF":7.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892488","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}
Cell reportsPub Date : 2024-12-24Epub Date: 2024-11-22DOI: 10.1016/j.celrep.2024.114992
Qin Ni, Zhuoxu Ge, Yizeng Li, Gabriel Shatkin, Jinyu Fu, Anindya Sen, Kaustav Bera, Yuhan Yang, Yichen Wang, Yufei Wu, Ana Carina Nogueira Vasconcelos, Yuqing Yan, Dingchang Lin, Andrew P Feinberg, Konstantinos Konstantopoulos, Sean X Sun
{"title":"Cytoskeletal activation of NHE1 regulates mechanosensitive cell volume adaptation and proliferation.","authors":"Qin Ni, Zhuoxu Ge, Yizeng Li, Gabriel Shatkin, Jinyu Fu, Anindya Sen, Kaustav Bera, Yuhan Yang, Yichen Wang, Yufei Wu, Ana Carina Nogueira Vasconcelos, Yuqing Yan, Dingchang Lin, Andrew P Feinberg, Konstantinos Konstantopoulos, Sean X Sun","doi":"10.1016/j.celrep.2024.114992","DOIUrl":"10.1016/j.celrep.2024.114992","url":null,"abstract":"<p><p>Mammalian cells rapidly respond to environmental changes by altering transmembrane water and ion fluxes, changing cell volume. Contractile forces generated by actomyosin have been proposed to mechanically regulate cell volume. However, our findings reveal a different mechanism in adherent cells, where elevated actomyosin activity increases cell volume in normal-like cells (NIH 3T3 and others) through interaction with the sodium-hydrogen exchanger isoform 1 (NHE1). This leads to a slow secondary volume increase (SVI) following the initial regulatory volume decrease during hypotonic shock. The active cell response is further confirmed by intracellular alkalinization during mechanical stretch. Moreover, cytoskeletal activation of NHE1 during SVI deforms the nucleus, causing immediate transcriptomic changes and ERK-dependent growth inhibition. Notably, SVI and its associated changes are absent in many cancer cell lines or cells on compliant substrates with reduced actomyosin activity. Thus, actomyosin acts as a sensory element rather than a force generator during adaptation to environmental challenges.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"114992"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695122","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}
Cell reportsPub Date : 2024-12-24Epub Date: 2024-11-28DOI: 10.1016/j.celrep.2024.115028
Wei Guo, Jie J Zhang, Jonathan P Newman, Matthew A Wilson
{"title":"Latent learning drives sleep-dependent plasticity in distinct CA1 subpopulations.","authors":"Wei Guo, Jie J Zhang, Jonathan P Newman, Matthew A Wilson","doi":"10.1016/j.celrep.2024.115028","DOIUrl":"10.1016/j.celrep.2024.115028","url":null,"abstract":"<p><p>Latent learning is a process that enables the brain to transform experiences into \"cognitive maps,\" a form of implicit memory, without requiring reinforced training. To investigate its neural mechanisms, we record from hippocampal neurons in mice during latent learning of spatial maps and observe that the high-dimensional neural state space gradually transforms into a low-dimensional manifold that closely resembles the physical environment. This transformation process is associated with the neural reactivation of navigational experiences during sleep. Additionally, we identify a subset of hippocampal neurons that, rather than forming place fields in a novel environment, maintain weak spatial tuning but gradually develop correlated activity with other neurons. The elevated correlation introduces redundancy into the ensemble code, transforming the neural state space into a low-dimensional manifold that effectively links discrete place fields of place cells into a map-like structure. These results suggest a potential mechanism for latent learning of spatial maps in the hippocampus.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"115028"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754864","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}
Cell reportsPub Date : 2024-12-24Epub Date: 2024-12-06DOI: 10.1016/j.celrep.2024.115036
Cara W Chao, Kaitlin R Sprouse, Marcos C Miranda, Nicholas J Catanzaro, Miranda L Hubbard, Amin Addetia, Cameron Stewart, Jack T Brown, Annie Dosey, Adian Valdez, Rashmi Ravichandran, Grace G Hendricks, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Jackson McGowan, Boston Simmons, Catherine Treichel, Isabelle Willoughby, Alexandra C Walls, Andrew T McGuire, Elizabeth M Leaf, Ralph S Baric, Alexandra Schäfer, David Veesler, Neil P King
{"title":"Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.","authors":"Cara W Chao, Kaitlin R Sprouse, Marcos C Miranda, Nicholas J Catanzaro, Miranda L Hubbard, Amin Addetia, Cameron Stewart, Jack T Brown, Annie Dosey, Adian Valdez, Rashmi Ravichandran, Grace G Hendricks, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Jackson McGowan, Boston Simmons, Catherine Treichel, Isabelle Willoughby, Alexandra C Walls, Andrew T McGuire, Elizabeth M Leaf, Ralph S Baric, Alexandra Schäfer, David Veesler, Neil P King","doi":"10.1016/j.celrep.2024.115036","DOIUrl":"10.1016/j.celrep.2024.115036","url":null,"abstract":"<p><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two-component nanoparticles displaying spike (S)-derived antigens induce neutralizing responses and protect mice against challenge with mouse-adapted MERS-CoV. Epitope mapping reveals the dominant responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle elicits antibodies targeting multiple non-overlapping epitopes in the RBD. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"115036"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791192","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}
Cell reportsPub Date : 2024-12-24Epub Date: 2024-12-10DOI: 10.1016/j.celrep.2024.115074
Zhigang Chen, Susu Tang, Xiangyi Xiao, Yizhou Hong, Boli Fu, Xuyi Li, Yuwei Shao, Liang Chen, Danhua Yuan, Yan Long, Hao Wang, Hao Hong
{"title":"Adiponectin receptor 1-mediated basolateral amygdala-prelimbic cortex circuit regulates methamphetamine-associated memory.","authors":"Zhigang Chen, Susu Tang, Xiangyi Xiao, Yizhou Hong, Boli Fu, Xuyi Li, Yuwei Shao, Liang Chen, Danhua Yuan, Yan Long, Hao Wang, Hao Hong","doi":"10.1016/j.celrep.2024.115074","DOIUrl":"10.1016/j.celrep.2024.115074","url":null,"abstract":"<p><p>The association between drug-induced rewards and environmental cues represents a promising strategy to address addiction. However, the neural networks and molecular mechanisms orchestrating methamphetamine (MA)-associated memories remain incompletely characterized. In this study, we demonstrated that AdipoRon (AR), a specific adiponectin receptor (AdipoR) agonist, inhibits the formation of MA-induced conditioned place preference (CPP) in MA-conditioned mice, accompanied by suppression of basolateral amygdala (BLA) CaMKIIα neuron activity. Furthermore, we identified an association between the excitatory circuit from the BLA to the prelimbic cortex (PrL) and the integration of MA-induced rewards with environmental cues. We also determined that the phosphorylated AMPK (p-AMPK)/Cav1.3 signaling pathway mediates the modulatory effects of AdipoR1 in PrL-projecting BLA CaMKIIα neurons on the formation of MA reward memories, a process influenced by physical exercise. These findings highlight the critical function of AdipoR1 in the BLA<sup>CaMKIIα</sup>→PrL<sup>CaMKIIα</sup> circuit in regulating MA-related memory formation, suggesting a potential target for managing MA use disorders.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"115074"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812201","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}
Cell reportsPub Date : 2024-12-24Epub Date: 2024-12-10DOI: 10.1016/j.celrep.2024.115045
Theo Crosson, Shreyas Bhat, Jo-Chiao Wang, Clara Salaun, Eleanne Fontaine, Katiane Roversi, Herbert Herzog, Moutih Rafei, Rikard Blunck, Sebastien Talbot
{"title":"Cytokines reprogram airway sensory neurons in asthma.","authors":"Theo Crosson, Shreyas Bhat, Jo-Chiao Wang, Clara Salaun, Eleanne Fontaine, Katiane Roversi, Herbert Herzog, Moutih Rafei, Rikard Blunck, Sebastien Talbot","doi":"10.1016/j.celrep.2024.115045","DOIUrl":"10.1016/j.celrep.2024.115045","url":null,"abstract":"<p><p>Nociceptor neurons play a crucial role in maintaining the body's homeostasis by detecting and responding to potential environmental dangers. However, this function can be detrimental during allergic reactions, as vagal nociceptors contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood. In this study, we investigate the changes in the molecular profile of airway nociceptor neurons during allergic airway inflammation and identify the signals driving such reprogramming. Using retrograde tracing and lineage reporting, we identify a specific class of inflammatory vagal nociceptor neurons that exclusively innervate the airways. In the ovalbumin mouse model of allergic airway inflammation, these neurons undergo significant reprogramming characterized by the upregulation of the neuropeptide Y (NPY) receptor Npy1r. A screening of cytokines and neurotrophins reveals that interleukin 1β (IL-1β), IL-13, and brain-derived neurotrophic factor (BDNF) drive part of this reprogramming. IL-13 triggers Npy1r overexpression in nociceptors via the JAK/STAT6 pathway. In parallel, NPY is released into the bronchoalveolar fluid of asthmatic mice, which limits the excitability of nociceptor neurons. Single-cell RNA sequencing of lung immune cells reveals that a cell-specific knockout of NPY1R in nociceptor neurons in asthmatic mice altered T cell infiltration. Opposite findings are observed in asthmatic mice in which nociceptor neurons are chemically ablated. In summary, allergic airway inflammation reprograms airway nociceptor neurons to acquire a pro-inflammatory phenotype, while a compensatory mechanism involving NPY1R limits the activity of nociceptor neurons.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"115045"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812203","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}
{"title":"Legionella uses host Rab GTPases and BAP31 to create a unique ER niche.","authors":"Attinder Chadha, Yu Yanai, Hiromu Oide, Yuichi Wakana, Hiroki Inoue, Saradindu Saha, Manish Paul, Mitsuo Tagaya, Kohei Arasaki, Shaeri Mukherjee","doi":"10.1016/j.celrep.2024.115053","DOIUrl":"10.1016/j.celrep.2024.115053","url":null,"abstract":"<p><p>The bacterium Legionella pneumophila secretes numerous effector proteins that manipulate endoplasmic reticulum (ER)-derived vesicles to form the Legionella-containing vacuole (LCV). Despite extensive studies, whether the LCV membrane is separate from or connected to the host ER network remains unclear. Here, we show that the smooth ER (sER) is closely associated with the LCV early in infection. Remarkably, Legionella forms a distinct rough ER (rER) niche at later stages, disconnected from the host ER network. We discover that host small GTPases Rab10 and Rab4 and an ER protein, BAP31, play crucial roles in transitioning the LCV from an sER to an rER. Additionally, we have identified a Legionella effector, Lpg1152, that binds to BAP31. Interestingly, the optimal growth of Legionella is dependent on both BAP31 and Lpg1152. These findings detail the complex interplay between host and pathogen in transforming the LCV membrane from a host-associated sER to a distinct rER.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"115053"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812205","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}
Cell reportsPub Date : 2024-12-24Epub Date: 2024-12-11DOI: 10.1016/j.celrep.2024.115008
Aditi Falnikar, Sebastian Quintremil, Hung-Jun Zhao, Haw-Yuan Cheng, Paige Helmer, Jin-Wu Tsai, Richard B Vallee
{"title":"The nucleoporin Nup153 is the anchor for Kif1a during basal nuclear migration in brain progenitor cells.","authors":"Aditi Falnikar, Sebastian Quintremil, Hung-Jun Zhao, Haw-Yuan Cheng, Paige Helmer, Jin-Wu Tsai, Richard B Vallee","doi":"10.1016/j.celrep.2024.115008","DOIUrl":"10.1016/j.celrep.2024.115008","url":null,"abstract":"<p><p>Radial glial progenitors (RGPs) are highly elongated epithelial cells that give rise to most stem cells, neurons, and glia in the vertebrate cerebral cortex. During development, the RGP nuclei exhibit a striking pattern of cell-cycle-dependent oscillatory movements known as interkinetic nuclear migration (INM), which we previously found to be mediated during G1 by the kinesin Kif1a and during G2 by cytoplasmic dynein, recruited to the nuclear envelope by the nucleoporins RanBP2 and Nup133. We now identify Nup153 as a nucleoporin anchor for Kif1a, responsible for G1-specific basal nuclear migration, providing a complete model for the mechanisms underlying this basic but mysterious behavior, with broad implications for understanding brain development.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 12","pages":"115008"},"PeriodicalIF":7.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817402","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}
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