Pub 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
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.
严格控制肿瘤微环境中 T 细胞的活性对产生保护性抗肿瘤免疫至关重要。然而，创造促进肿瘤浸润 T 细胞的关键成纤维细胞龛的细胞的身份、分化和功能仍然难以捉摸。在这里，我们发现表达 CCL19 的成纤维网状细胞（FRC）在人类非小细胞肺癌中产生了相互连接的 T 细胞环境（TE），包括三级淋巴结构和 T 细胞轨道。对TEs中FRC-T细胞相互作用组的分析表明，分子网络调控着表达CCL19的成纤维细胞和T细胞活化途径的龛特异性分化。对小鼠进行的单细胞转录组学和细胞命运图谱分析证实，TE 中的成纤维细胞起源于壁细胞和临近细胞的祖细胞。瘤内 FRC 前体的消融降低了抗肿瘤 T 细胞的活性，从而导致冠状病毒载体免疫疗法的肿瘤控制率降低。总之，肿瘤微环境中特化的 FRC 龛决定着抗肿瘤 T 细胞免疫的质量和程度。
{"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}
Pub 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
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.
一般来说，味觉对长时间甜味刺激的敏感性会降低，这被称为甜味适应。然而，其机理图谱仍不完整。在这里，我们报告了神经胶质样 I 型细胞通过与化学感觉 II 型细胞的细胞间串扰提供了一种独特的甜味适应模式。利用基于微流控的舌内成像系统，我们发现甜味适应是通过 II 型细胞到味觉传入神经的突触传导来促进的，而 I 型细胞则表现出时间延迟和延长的活动。我们发现 I 型细胞通过 P2RY2 接收相邻 II 型细胞的嘌呤能输入，并为甜味的突触传导提供抑制反馈。与我们在细胞水平上的发现一致，I型细胞的嘌呤能激活减弱了甜味舔食行为，P2RY2基因敲除小鼠的适应行为减慢。我们的研究突显了一种隐蔽的细胞间甜味适应模式，它可能有助于对延长的甜味进行有效编码。
{"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}
Pub Date : 2024-11-15DOI: 10.1016/j.cell.2024.10.031
Desheng Zeng, Junqing Lv, Xu Li, Hongtao Liu
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 Arabidopsis 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.
{"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}
Pub 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
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.
{"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}
Pub 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
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 cis-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.
{"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}
Pub 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
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.
{"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}
Pub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.043
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 Cell’s 50th 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.
{"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}
Pub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.025
Yu Ding, Boxun Lu
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.
{"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}
Pub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.026
Job Dekker, Leonid A. Mirny
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.
{"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}
Pub Date : 2024-11-14DOI: 10.1016/j.cell.2024.10.029
Stephen R. Quake
In this essay, I will put forth what I see as a major conceptual challenge for biology in the next decade, one that is inspired by Crick’s Central Dogma: understanding information flow in the cell in the most general sense.
{"title":"The cellular dogma","authors":"Stephen R. Quake","doi":"10.1016/j.cell.2024.10.029","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.029","url":null,"abstract":"In this essay, I will put forth what I see as a major conceptual challenge for biology in the next decade, one that is inspired by Crick’s Central Dogma: understanding information flow in the cell in the most general sense.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"16 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610153","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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