CellPub Date : 2024-11-20DOI: 10.1016/j.cell.2024.10.049
France Denoeud, Olivier Godfroy, Corinne Cruaud, Svenja Heesch, Zofia Nehr, Nachida Tadrent, Arnaud Couloux, Loraine Brillet-Guéguen, Ludovic Delage, Dean Mckeown, Taizo Motomura, Duncan Sussfeld, Xiao Fan, Lisa Mazéas, Nicolas Terrapon, Josué Barrera-Redondo, Romy Petroll, Lauric Reynes, Seok-Wan Choi, Jihoon Jo, J. Mark Cock
{"title":"Evolutionary genomics of the emergence of brown algae as key components of coastal ecosystems","authors":"France Denoeud, Olivier Godfroy, Corinne Cruaud, Svenja Heesch, Zofia Nehr, Nachida Tadrent, Arnaud Couloux, Loraine Brillet-Guéguen, Ludovic Delage, Dean Mckeown, Taizo Motomura, Duncan Sussfeld, Xiao Fan, Lisa Mazéas, Nicolas Terrapon, Josué Barrera-Redondo, Romy Petroll, Lauric Reynes, Seok-Wan Choi, Jihoon Jo, J. Mark Cock","doi":"10.1016/j.cell.2024.10.049","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.049","url":null,"abstract":"Brown seaweeds are keystone species of coastal ecosystems, often forming extensive underwater forests, and are under considerable threat from climate change. In this study, analysis of multiple genomes has provided insights across the entire evolutionary history of this lineage, from initial emergence, through later diversification of the brown algal orders, down to microevolutionary events at the genus level. Emergence of the brown algal lineage was associated with a marked gain of new orthologous gene families, enhanced protein domain rearrangement, increased horizontal gene transfer events, and the acquisition of novel signaling molecules and key metabolic pathways, the latter notably related to biosynthesis of the alginate-based extracellular matrix, and halogen and phlorotannin biosynthesis. We show that brown algal genome diversification is tightly linked to phenotypic divergence, including changes in life cycle strategy and zoid flagellar structure. The study also showed that integration of large viral genomes has had a significant impact on brown algal genome content throughout the emergence of the lineage.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"64 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673166","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}
CellPub Date : 2024-11-19DOI: 10.1016/j.cell.2024.10.042
Lucas Onder, Chrysa Papadopoulou, Almut Lütge, Hung-Wei Cheng, Mechthild Lütge, Christian Perez-Shibayama, Cristina Gil-Cruz, Angelina De Martin, Lisa Kurz, Nadine Cadosch, Natalia B. Pikor, Regulo Rodriguez, Diana Born, Wolfram Jochum, Pawel Leskow, Andre Dutly, Mark D. Robinson, Burkhard Ludewig
{"title":"Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer","authors":"Lucas Onder, Chrysa Papadopoulou, Almut Lütge, Hung-Wei Cheng, Mechthild Lütge, Christian Perez-Shibayama, Cristina Gil-Cruz, Angelina De Martin, Lisa Kurz, Nadine Cadosch, Natalia B. Pikor, Regulo Rodriguez, Diana Born, Wolfram Jochum, Pawel Leskow, Andre Dutly, Mark D. Robinson, Burkhard Ludewig","doi":"10.1016/j.cell.2024.10.042","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.042","url":null,"abstract":"Stringent control of T cell activity in the tumor microenvironment is essential for the generation of protective antitumor immunity. However, the identity, differentiation, and functions of the cells that create critical fibroblastic niches promoting tumor-infiltrating T cells remain elusive. Here, we show that CCL19-expressing fibroblastic reticular cells (FRCs) generate interconnected T cell environments (TEs) in human non-small cell lung cancer, including tertiary lymphoid structures and T cell tracks. Analysis of the FRC-T cell interactome in TEs indicated molecular networks regulating niche-specific differentiation of CCL19-expressing fibroblasts and T cell activation pathways. Single-cell transcriptomics and cell fate-mapping analyses in mice confirmed that FRCs in TEs originate from mural and adventitial progenitors. Ablation of intratumoral FRC precursors decreased antitumor T cell activity, resulting in reduced tumor control during coronavirus vector-based immunotherapy. In summary, specialized FRC niches in the tumor microenvironment govern the quality and extent of antitumor T cell immunity.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"18 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673168","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}
CellPub Date : 2024-11-18DOI: 10.1016/j.cell.2024.10.041
Gha Yeon Park, Geehyun Lee, Jongmin Yoon, Jisoo Han, Pyonggang Choi, Minjae Kim, Sungho Lee, Chaeri Park, Zhaofa Wu, Yulong Li, Myunghwan Choi
{"title":"Glia-like taste cells mediate an intercellular mode of peripheral sweet adaptation","authors":"Gha Yeon Park, Geehyun Lee, Jongmin Yoon, Jisoo Han, Pyonggang Choi, Minjae Kim, Sungho Lee, Chaeri Park, Zhaofa Wu, Yulong Li, Myunghwan Choi","doi":"10.1016/j.cell.2024.10.041","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.041","url":null,"abstract":"The sense of taste generally shows diminishing sensitivity to prolonged sweet stimuli, referred to as sweet adaptation. Yet, its mechanistic landscape remains incomplete. Here, we report that glia-like type I cells provide a distinct mode of sweet adaptation via intercellular crosstalk with chemosensory type II cells. Using the microfluidic-based intravital tongue imaging system, we found that sweet adaptation is facilitated along the synaptic transduction from type II cells to gustatory afferent nerves, while type I cells display temporally delayed and prolonged activities. We identified that type I cells receive purinergic input from adjacent type II cells via P2RY2 and provide inhibitory feedback to the synaptic transduction of sweet taste. Aligning with our cellular-level findings, purinergic activation of type I cells attenuated sweet licking behavior, and P2RY2 knockout mice showed decelerated adaptation behavior. Our study highlights a veiled intercellular mode of sweet adaptation, potentially contributing to the efficient encoding of prolonged sweetness.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"21 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665531","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}
CellPub Date : 2024-11-15DOI: 10.1016/j.cell.2024.10.031
Desheng Zeng, Junqing Lv, Xu Li, Hongtao Liu
{"title":"The Arabidopsis blue-light photoreceptor CRY2 is active in darkness to inhibit root growth","authors":"Desheng Zeng, Junqing Lv, Xu Li, Hongtao Liu","doi":"10.1016/j.cell.2024.10.031","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.031","url":null,"abstract":"Cryptochromes (CRYs) are blue-light receptors that regulate diverse aspects of plant growth. However, whether and how non-photoexcited CRYs function in darkness or non-blue-light conditions is unknown. Here, we show that CRY2 affects the <em>Arabidopsis</em> transcriptome even in darkness, revealing a non-canonical function. CRY2 suppresses cell division in the root apical meristem to downregulate root elongation in darkness. Blue-light oligomerizes CRY2 to de-repress root elongation. CRY2 physically interacts with FORKED-LIKE 1 (FL1) and FL3, and these interactions are inhibited by blue light, with only monomeric but not dimeric CRY2 able to interact. FL1 and FL3 associate with the chromatin of cell division genes to facilitate their transcription. This pro-growth activity is inhibited by CRY2’s physical interaction with FLs in darkness. Plants have evolved to perceive both blue-light and dark cues to coordinate activation and repression of competing developmental processes in above- and below-ground organs through economical and dichotomous use of ancient light receptors.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"45 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637595","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}
CellPub Date : 2024-11-15DOI: 10.1016/j.cell.2024.10.034
Sylvie L. Lesuis, Sungmo Park, Annelies Hoorn, Asim J. Rashid, Andrew J. Mocle, Eric W. Salter, Stefan Vislavski, Madison T. Gray, Angelica M. Torelli, Antonietta DeCristofaro, Wouter P.F. Driever, Mario van der Stelt, Larry S. Zweifel, Graham L. Collingridge, Julie L. Lefebvre, Brandon J. Walters, Paul W. Frankland, Matthew N. Hill, Sheena A. Josselyn
{"title":"Stress disrupts engram ensembles in lateral amygdala to generalize threat memory in mice","authors":"Sylvie L. Lesuis, Sungmo Park, Annelies Hoorn, Asim J. Rashid, Andrew J. Mocle, Eric W. Salter, Stefan Vislavski, Madison T. Gray, Angelica M. Torelli, Antonietta DeCristofaro, Wouter P.F. Driever, Mario van der Stelt, Larry S. Zweifel, Graham L. Collingridge, Julie L. Lefebvre, Brandon J. Walters, Paul W. Frankland, Matthew N. Hill, Sheena A. Josselyn","doi":"10.1016/j.cell.2024.10.034","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.034","url":null,"abstract":"Stress induces aversive memory overgeneralization, a hallmark of many psychiatric disorders. Memories are encoded by a sparse ensemble of neurons active during an event (an engram ensemble). We examined the molecular and circuit processes mediating stress-induced threat memory overgeneralization in mice. Stress, acting via corticosterone, increased the density of engram ensembles supporting a threat memory in lateral amygdala, and this engram ensemble was reactivated by both specific and non-specific retrieval cues (generalized threat memory). Furthermore, we identified a critical role for endocannabinoids, acting retrogradely on parvalbumin-positive (PV+) lateral amygdala interneurons in the formation of a less-sparse engram and memory generalization induced by stress. Glucocorticoid receptor antagonists, endocannabinoid synthesis inhibitors, increasing PV+ neuronal activity, and knocking down cannabinoid receptors in lateral amygdala PV+ neurons restored threat memory specificity and a sparse engram in stressed mice. These findings offer insights into stress-induced memory alterations, providing potential therapeutic avenues for stress-related disorders.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"11 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637592","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}
CellPub Date : 2024-11-15DOI: 10.1016/j.cell.2024.10.039
Megan S. Ostrowski, Marty G. Yang, Colin P. McNally, Nour J. Abdulhay, Simai Wang, Keerthi Renduchintala, Iryna Irkliyenko, Alva Biran, Brandon T.L. Chew, Ayush D. Midha, Emily V. Wong, Jonathan Sandoval, Isha H. Jain, Anja Groth, Elphège P. Nora, Hani Goodarzi, Vijay Ramani
{"title":"The single-molecule accessibility landscape of newly replicated mammalian chromatin","authors":"Megan S. Ostrowski, Marty G. Yang, Colin P. McNally, Nour J. Abdulhay, Simai Wang, Keerthi Renduchintala, Iryna Irkliyenko, Alva Biran, Brandon T.L. Chew, Ayush D. Midha, Emily V. Wong, Jonathan Sandoval, Isha H. Jain, Anja Groth, Elphège P. Nora, Hani Goodarzi, Vijay Ramani","doi":"10.1016/j.cell.2024.10.039","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.039","url":null,"abstract":"We present replication-aware single-molecule accessibility mapping (RASAM), a method to nondestructively measure replication status and protein-DNA interactions on chromatin genome-wide. Using RASAM, we uncover a genome-wide state of single-molecule “hyperaccessibility” post-replication that resolves over several hours. Combining RASAM with cellular models for rapid protein degradation, we demonstrate that histone chaperone CAF-1 reduces nascent chromatin accessibility by filling single-molecular “gaps” and generating closely spaced dinucleosomes on replicated DNA. At <em>cis</em>-regulatory elements, we observe unique modes by which nascent chromatin hyperaccessibility resolves: at CCCTC-binding factor (CTCF)-binding sites, CTCF and nucleosomes compete, reducing CTCF occupancy and motif accessibility post-replication; at active transcription start sites, high chromatin accessibility is maintained, implying rapid re-establishment of nucleosome-free regions. Our study introduces a new paradigm for studying replicated chromatin fiber organization. More broadly, we uncover a unique organization of newly replicated chromatin that must be reset by active processes, providing a substrate for epigenetic reprogramming.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"7 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637593","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}
CellPub Date : 2024-11-15DOI: 10.1016/j.cell.2024.10.040
Daniel Richard, Pushpanathan Muthuirulan, Mariel Young, Loic Yengo, Sailaja Vedantam, Eirini Marouli, Eric Bartell, Joel Hirschhorn, Terence D. Capellini
{"title":"Functional genomics of human skeletal development and the patterning of height heritability","authors":"Daniel Richard, Pushpanathan Muthuirulan, Mariel Young, Loic Yengo, Sailaja Vedantam, Eirini Marouli, Eric Bartell, Joel Hirschhorn, Terence D. Capellini","doi":"10.1016/j.cell.2024.10.040","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.040","url":null,"abstract":"Underlying variation in height are regulatory changes to chondrocytes, cartilage cells comprising long-bone growth plates. Currently, we lack knowledge on epigenetic regulation and gene expression of chondrocytes sampled across the human skeleton, and therefore we cannot understand basic regulatory mechanisms controlling height biology. We first rectify this issue by generating extensive epigenetic and transcriptomic maps from chondrocytes sampled from different growth plates across developing human skeletons, discovering novel regulatory networks shaping human bone/joint development. Next, using these maps in tandem with height genome-wide association study (GWAS) signals, we disentangle the regulatory impacts that skeletal element-specific versus global-acting variants have on skeletal growth, revealing the prime importance of regulatory pleiotropy in controlling height variation. Finally, as height is highly heritable, and thus often the test case for complex-trait genetics, we leverage these datasets within a testable omnigenic model framework to discover novel chondrocyte developmental modules and peripheral-acting factors shaping height biology and skeletal growth.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"98 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637876","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}
CellPub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.043
{"title":"Molecular biology: The fundamental science fueling innovation","authors":"","doi":"10.1016/j.cell.2024.10.043","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.043","url":null,"abstract":"Molecular biology aims to understand the details of life by focusing closely on biopolymers—DNAs, RNAs, and proteins—and how they interact with one another. Advances in this field have enabled dazzling achievements in virtually all areas of biological, biomedical, and clinical sciences. As we draw near to the conclusion of <em>Cell</em>’s 50<sup>th</sup> anniversary, we celebrate the wonders of molecular biology and look ahead to the exciting path forward for a branch of science that is driven by curiosity and has always been an integral part of the journal.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"57 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610146","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}
CellPub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.025
Yu Ding, Boxun Lu
{"title":"SnapShot: Targeted protein degradation","authors":"Yu Ding, Boxun Lu","doi":"10.1016/j.cell.2024.10.025","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.025","url":null,"abstract":"Targeted protein degradation strategies leverage endogenous cellular degradation machinery to selectively eliminate a protein of interest. Emerging technologies are opening avenues in drug discovery and functional characterization of intracellular, membrane, and extracellular proteins. To view this SnapShot, open or download the PDF.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"11 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610144","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}
CellPub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.026
Job Dekker, Leonid A. Mirny
{"title":"The chromosome folding problem and how cells solve it","authors":"Job Dekker, Leonid A. Mirny","doi":"10.1016/j.cell.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.026","url":null,"abstract":"Every cell must solve the problem of how to fold its genome. We describe how the folded state of chromosomes is the result of the combined activity of multiple conserved mechanisms. Homotypic affinity-driven interactions lead to spatial partitioning of active and inactive loci. Molecular motors fold chromosomes through loop extrusion. Topological features such as supercoiling and entanglements contribute to chromosome folding and its dynamics, and tethering loci to sub-nuclear structures adds additional constraints. Dramatically diverse chromosome conformations observed throughout the cell cycle and across the tree of life can be explained through differential regulation and implementation of these basic mechanisms. We propose that the first functions of chromosome folding are to mediate genome replication, compaction, and segregation and that mechanisms of folding have subsequently been co-opted for other roles, including long-range gene regulation, in different conditions, cell types, and species.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"127 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610148","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}