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An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania 一种古老的 HLA I 类受体等位基因使大洋洲原住民的自然杀伤细胞驱动免疫多样化
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-29 DOI: 10.1016/j.cell.2024.10.005
Liyen Loh, Philippa M. Saunders, Camilla Faoro, Neus Font-Porterias, Neda Nemat-Gorgani, Genelle F. Harrison, Suraju Sadeeq, Luca Hensen, Shu Cheng Wong, Jacqueline Widjaja, E. Bridie Clemens, Shiying Zhu, Katherine M. Kichula, Sudan Tao, Faming Zhu, Gonzalo Montero-Martin, Marcelo Fernandez-Vina, Lisbeth A. Guethlein, Julian P. Vivian, Jane Davies, Paul J. Norman
{"title":"An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania","authors":"Liyen Loh, Philippa M. Saunders, Camilla Faoro, Neus Font-Porterias, Neda Nemat-Gorgani, Genelle F. Harrison, Suraju Sadeeq, Luca Hensen, Shu Cheng Wong, Jacqueline Widjaja, E. Bridie Clemens, Shiying Zhu, Katherine M. Kichula, Sudan Tao, Faming Zhu, Gonzalo Montero-Martin, Marcelo Fernandez-Vina, Lisbeth A. Guethlein, Julian P. Vivian, Jane Davies, Paul J. Norman","doi":"10.1016/j.cell.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.005","url":null,"abstract":"Genetic variation in host immunity impacts the disproportionate burden of infectious diseases that can be experienced by First Nations peoples. Polymorphic human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) are key regulators of natural killer (NK) cells, which mediate early infection control. How this variation impacts their responses across populations is unclear. We show that HLA-A<sup>∗</sup>24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1<sup>∗</sup>114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1<sup>∗</sup>114<sup>+</sup>NK cells from First Nations Australian donors are inhibited through binding HLA-A<sup>∗</sup>24:02. The KIR3DL1<sup>∗</sup>114 lineage is defined by phenylalanine at residue 166. Structural and binding studies show phenylalanine 166 forms multiple unique contacts with HLA-peptide complexes, increasing both affinity and specificity. Accordingly, assessing immunogenetic variation and the functional implications for immunity are fundamental toward understanding population-based disease associations.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"103 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536565","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
Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch 在结构指导下发现用于治疗肝病且不会引起瘙痒的胆汁酸衍生物
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-29 DOI: 10.1016/j.cell.2024.10.001
Jun Yang, Tianjun Zhao, Junping Fan, Huaibin Zou, Guangyi Lan, Fusheng Guo, Yaocheng Shi, Han Ke, Huasheng Yu, Zongwei Yue, Xin Wang, Yingjie Bai, Shuai Li, Yingjun Liu, Xiaoming Wang, Yu Chen, Yulong Li, Xiaoguang Lei
{"title":"Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch","authors":"Jun Yang, Tianjun Zhao, Junping Fan, Huaibin Zou, Guangyi Lan, Fusheng Guo, Yaocheng Shi, Han Ke, Huasheng Yu, Zongwei Yue, Xin Wang, Yingjie Bai, Shuai Li, Yingjun Liu, Xiaoming Wang, Yu Chen, Yulong Li, Xiaoguang Lei","doi":"10.1016/j.cell.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.001","url":null,"abstract":"Chronic itch is a debilitating symptom profoundly impacting the quality of life in patients with liver diseases like cholestasis. Activation of the human G-protein coupled receptor, MRGPRX4 (hX4), by bile acids (BAs) is implicated in promoting cholestasis itch. However, the detailed underlying mechanisms remain elusive. Here, we identified 3-sulfated BAs that are elevated in cholestatic patients with itch symptoms. We solved the cryo-EM structure of hX4-Gq in a complex with 3-phosphated deoxycholic acid (DCA-3P), a mimic of the endogenous 3-sulfated deoxycholic acid (DCA-3S). This structure revealed an unprecedented ligand-binding pocket in MRGPR family proteins, highlighting the crucial role of the 3-hydroxyl (3-OH) group on BAs in activating hX4. Guided by this structural information, we designed and developed compound 7 (C7), a BA derivative lacking the 3-OH. Notably, C7 effectively alleviates hepatic injury and fibrosis in liver disease models while significantly mitigating the itch side effects.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"237 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536564","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
Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration 干细胞活动与内源性逆转录病毒的抑制共同作用于成人组织再生
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-29 DOI: 10.1016/j.cell.2024.10.007
Ying Lyu, Soo Jin Kim, Ericka S. Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N. Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H. Hassan, Miranda L. Johnson, Lisa P. Deliu, Yun You, Anurag Sharma, Yejing Ge
{"title":"Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration","authors":"Ying Lyu, Soo Jin Kim, Ericka S. Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N. Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H. Hassan, Miranda L. Johnson, Lisa P. Deliu, Yun You, Anurag Sharma, Yejing Ge","doi":"10.1016/j.cell.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.007","url":null,"abstract":"Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in murine skin. SETDB1 ablation leads to the reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and the assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair follicle stem cells and progenitors and antiviral-independent response due to replication stress in transient amplifying cells. ERV reactivation is promoted by DNA demethylase ten-eleven translocation (TET)-mediated hydroxymethylation and recapitulated by ablating cell fate transcription factors. Together, we demonstrated ERV silencing is coupled with stem cell activity and essential for adult hair regeneration.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"132 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536563","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
Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques 在以融合肽为前体的 SHIV 感染猕猴体内发挥强效、广泛的 HIV-1 中和作用
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-28 DOI: 10.1016/j.cell.2024.10.003
Hua Wang, Cheng Cheng, James L. Dal Santo, Chen-Hsiang Shen, Tatsiana Bylund, Amy R. Henry, Colin A. Howe, Juyun Hwang, Nicholas C. Morano, Daniel J. Morris, Sergei Pletnev, Ryan S. Roark, Tongqing Zhou, Bryan T. Hansen, Forrest H. Hoyt, Timothy S. Johnston, Shuyi Wang, Baoshan Zhang, David R. Ambrozak, Jordan E. Becker, Peter D. Kwong
{"title":"Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques","authors":"Hua Wang, Cheng Cheng, James L. Dal Santo, Chen-Hsiang Shen, Tatsiana Bylund, Amy R. Henry, Colin A. Howe, Juyun Hwang, Nicholas C. Morano, Daniel J. Morris, Sergei Pletnev, Ryan S. Roark, Tongqing Zhou, Bryan T. Hansen, Forrest H. Hoyt, Timothy S. Johnston, Shuyi Wang, Baoshan Zhang, David R. Ambrozak, Jordan E. Becker, Peter D. Kwong","doi":"10.1016/j.cell.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.003","url":null,"abstract":"An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%–77% breadth (geometric mean 50% inhibitory dilution [ID<sub>50</sub>] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%–60% (50% inhibitory concentration [IC<sub>50</sub>] &lt; 50 μg/mL) and total lineage-concentrations estimates of 50–200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide <em>in vivo</em> molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"9 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519571","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
Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer 多参数成像揭示头颈癌中与临床相关的癌细胞-基质相互作用动态
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-28 DOI: 10.1016/j.cell.2024.09.046
Karolina Punovuori, Fabien Bertillot, Yekaterina A. Miroshnikova, Mirjam I. Binner, Satu-Marja Myllymäki, Gautier Follain, Kai Kruse, Johannes Routila, Teemu Huusko, Teijo Pellinen, Jaana Hagström, Noemi Kedei, Sami Ventelä, Antti Mäkitie, Johanna Ivaska, Sara A. Wickström
{"title":"Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer","authors":"Karolina Punovuori, Fabien Bertillot, Yekaterina A. Miroshnikova, Mirjam I. Binner, Satu-Marja Myllymäki, Gautier Follain, Kai Kruse, Johannes Routila, Teemu Huusko, Teijo Pellinen, Jaana Hagström, Noemi Kedei, Sami Ventelä, Antti Mäkitie, Johanna Ivaska, Sara A. Wickström","doi":"10.1016/j.cell.2024.09.046","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.046","url":null,"abstract":"Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution. By combining cell-state markers with morphological features, we identify phenotypic signatures that correlate with clinical features, including metastasis and recurrence. Integration of tumor and stromal signatures reveals that partial epithelial-mesenchymal transition (pEMT) renders disease outcome highly sensitive to stromal composition, generating a strong prognostic and predictive signature. Spatial transcriptomics and subsequent analyses of cancer spheroid dynamics identify the cancer-associated fibroblast-pEMT axis as a nexus for intercompartmental signaling that reprograms pEMT cells into an invasive phenotype. Taken together, we establish a paradigm to identify clinically relevant tumor phenotypes and discover a cell-state-dependent interplay between stromal and epithelial compartments that drives cancer aggression.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519570","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 CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity CRISPR相关腺苷脱氨酶Cad1将ATP转化为ITP,提供抗病毒免疫力
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-28 DOI: 10.1016/j.cell.2024.10.002
Christian F. Baca, Puja Majumder, James H. Hickling, Linzhi Ye, Marianna Teplova, Sean F. Brady, Dinshaw J. Patel, Luciano A. Marraffini
{"title":"The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity","authors":"Christian F. Baca, Puja Majumder, James H. Hickling, Linzhi Ye, Marianna Teplova, Sean F. Brady, Dinshaw J. Patel, Luciano A. Marraffini","doi":"10.1016/j.cell.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.002","url":null,"abstract":"Type III CRISPR systems provide immunity against genetic invaders through the production of cyclic oligo-adenylate (cA<sub>n</sub>) molecules that activate effector proteins that contain CRISPR-associated Rossman fold (CARF) domains. Here, we characterized the function and structure of an effector in which the CARF domain is fused to an adenosine deaminase domain, CRISPR-associated adenosine deaminase 1 (Cad1). We show that upon binding of cA<sub>4</sub> or cA<sub>6</sub> to its CARF domain, Cad1 converts ATP to ITP, both <em>in vivo</em> and <em>in vitro</em>. Cryoelectron microscopy (cryo-EM) structural studies on full-length Cad1 reveal an hexameric assembly composed of a trimer of dimers, with bound ATP at inter-domain sites required for activity and ATP/ITP within deaminase active sites. Upon synthesis of cA<sub>n</sub> during phage infection, Cad1 activation leads to a growth arrest of the host that prevents viral propagation. Our findings reveal that CRISPR-Cas systems employ a wide range of molecular mechanisms beyond nucleic acid degradation to provide adaptive immunity in prokaryotes.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"109 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519573","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
Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice 副猪链球菌促进小鼠胃部炎症、萎缩和肿瘤发生
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-26 DOI: 10.1016/j.cell.2024.10.036
Kaili Fu, Alvin Ho Kwan Cheung, Chi Chun Wong, Weixin Liu, Yunfei Zhou, Feixue Wang, Pingmei Huang, Kai Yuan, Olabisi Oluwabukola Coker, Yasi Pan, Danyu Chen, Nga Man Lam, Mengxue Gao, Xiang Zhang, He Huang, Ka Fai To, Joseph Jao Yiu Sung, Jun Yu
{"title":"Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice","authors":"Kaili Fu, Alvin Ho Kwan Cheung, Chi Chun Wong, Weixin Liu, Yunfei Zhou, Feixue Wang, Pingmei Huang, Kai Yuan, Olabisi Oluwabukola Coker, Yasi Pan, Danyu Chen, Nga Man Lam, Mengxue Gao, Xiang Zhang, He Huang, Ka Fai To, Joseph Jao Yiu Sung, Jun Yu","doi":"10.1016/j.cell.2024.10.036","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.036","url":null,"abstract":"(Cell <em>187</em>, 882–896.e1–e17; February 15, 2024)","PeriodicalId":9656,"journal":{"name":"Cell","volume":"1 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490646","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
Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018–2024: Predominance of zoonotic transmission 2018-2024 年刚果民主共和国 I 支 mpox 病毒基因组多样性:人畜共患病传播占主导地位
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-24 DOI: 10.1016/j.cell.2024.10.017
Eddy Kinganda-Lusamaki, Adrienne Amuri-Aziza, Nicolas Fernandez-Nuñez, Jean-Claude Makangara-Cigolo, Catherine Pratt, Emmanuel Hasivirwe Vakaniaki, Nicole A. Hoff, Gradi Luakanda-Ndelemo, Prince Akil-Bandali, Sabin Sabiti Nundu, Noella Mulopo-Mukanya, Michel Ngimba, Brigitte Modadra-Madakpa, Ruth Diavita, Princesse Paku-Tshambu, Elisabeth Pukuta-Simbu, Sydney Merritt, Áine O’Toole, Nicola Low, Antoine Nkuba-Ndaye, Steve Ahuka-Mundeke
{"title":"Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018–2024: Predominance of zoonotic transmission","authors":"Eddy Kinganda-Lusamaki, Adrienne Amuri-Aziza, Nicolas Fernandez-Nuñez, Jean-Claude Makangara-Cigolo, Catherine Pratt, Emmanuel Hasivirwe Vakaniaki, Nicole A. Hoff, Gradi Luakanda-Ndelemo, Prince Akil-Bandali, Sabin Sabiti Nundu, Noella Mulopo-Mukanya, Michel Ngimba, Brigitte Modadra-Madakpa, Ruth Diavita, Princesse Paku-Tshambu, Elisabeth Pukuta-Simbu, Sydney Merritt, Áine O’Toole, Nicola Low, Antoine Nkuba-Ndaye, Steve Ahuka-Mundeke","doi":"10.1016/j.cell.2024.10.017","DOIUrl":"https://doi.org/10.1016/j.cell.2024.10.017","url":null,"abstract":"Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC). High-quality genomes were generated for 337 patients from 14/26 provinces to document whether the increase in number of cases is due to zoonotic spillover events or viral evolution, with enrichment of APOBEC3 mutations linked to human adaptation. Our study highlights two patterns of transmission contributing to the source of human cases. All new sequences from the eastern South Kivu province (<em>n</em> = 17; 4.8%) corresponded to the recently described clade Ib, associated with sexual contact and sustained human-to-human transmission. By contrast, all other genomes are clade Ia, which exhibits high genetic diversity with low numbers of APOBEC3 mutations compared with clade Ib, suggesting multiple zoonotic introductions. The presence of multiple clade I variants in urban areas highlights the need for coordinated international response efforts and more studies on the transmission and the reservoir of mpox.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"125 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489211","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
Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3 海马 CA3 区记忆支持神经元动力学机制
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-24 DOI: 10.1016/j.cell.2024.09.041
Yiding Li, John J. Briguglio, Sandro Romani, Jeffrey C. Magee
{"title":"Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3","authors":"Yiding Li, John J. Briguglio, Sandro Romani, Jeffrey C. Magee","doi":"10.1016/j.cell.2024.09.041","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.041","url":null,"abstract":"Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular V<sub>m</sub> recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not the DG was required to update place cell activity based on the animal’s movement. These data were captured by a computational model that used BTSP and an external updating input to produce attractor dynamics under online learning conditions. Theoretical analyses further highlight the superior memory storage capacity of such networks, especially when dealing with correlated input patterns. This evidence elucidates the cellular and circuit mechanisms of learning and memory formation in the hippocampus.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"5 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489059","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 multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors 多模态斑马鱼发育图谱揭示了晚期脊椎动物多能轴突祖细胞的状态转换动力学
IF 64.5 1区 生物学
Cell Pub Date : 2024-10-24 DOI: 10.1016/j.cell.2024.09.047
Merlin Lange, Alejandro Granados, Shruthi VijayKumar, Jordão Bragantini, Sarah Ancheta, Yang-Joon Kim, Sreejith Santhosh, Michael Borja, Hirofumi Kobayashi, Erin McGeever, Ahmet Can Solak, Bin Yang, Xiang Zhao, Yang Liu, Angela M. Detweiler, Sheryl Paul, Ilan Theodoro, Honey Mekonen, Chris Charlton, Tiger Lao, Loïc A. Royer
{"title":"A multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors","authors":"Merlin Lange, Alejandro Granados, Shruthi VijayKumar, Jordão Bragantini, Sarah Ancheta, Yang-Joon Kim, Sreejith Santhosh, Michael Borja, Hirofumi Kobayashi, Erin McGeever, Ahmet Can Solak, Bin Yang, Xiang Zhao, Yang Liu, Angela M. Detweiler, Sheryl Paul, Ilan Theodoro, Honey Mekonen, Chris Charlton, Tiger Lao, Loïc A. Royer","doi":"10.1016/j.cell.2024.09.047","DOIUrl":"https://doi.org/10.1016/j.cell.2024.09.047","url":null,"abstract":"Elucidating organismal developmental processes requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by reconstructions of cellular trajectories. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling <em>in silico</em> fate-mapping experiments. To demonstrate the versatility of our multimodal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of neuro-mesodermal progenitors (NMPs) and the origins of a joint kidney-hemangioblast progenitor population.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"5 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489061","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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