Cell reports最新文献_第4页

Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons. 组合转录调节在听觉神经元中建立适合亚型的突触特性。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-06 DOI: 10.1016/j.celrep.2025.115796

Isle Bastille, Lucy Lee, Cynthia Moncada-Reid, Wei-Ming Yu, Austen Sitko, Andrea Yung, Mina Zamani, Nele Christophersen, Reza Maroofian, Hamid Galehdari, Norbert Babai, Barbara Vona, Tobias Moser, Lisa Goodrich

{"title":"Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons.","authors":"Isle Bastille, Lucy Lee, Cynthia Moncada-Reid, Wei-Ming Yu, Austen Sitko, Andrea Yung, Mina Zamani, Nele Christophersen, Reza Maroofian, Hamid Galehdari, Norbert Babai, Barbara Vona, Tobias Moser, Lisa Goodrich","doi":"10.1016/j.celrep.2025.115796","DOIUrl":"10.1016/j.celrep.2025.115796","url":null,"abstract":"Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity are known, it remains unclear how synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three spiral ganglion neuron (SGN) subtypes that collectively encode sound. Here, we demonstrate that Maf transcription factors combinatorially shape synaptic properties in SGNs. SGN subtypes express different ratios of c-Maf and Mafb, which act redundantly to impart subtype identities and individually to shape subtype-appropriate gene expression programs. On their own, c-Maf and Mafb have independent and opposing effects on synaptic features and hearing. A mutation in the MAFB leucine zipper domain causes deafness in humans, underscoring the importance of regulated Maf activity for hearing. Thus, functional diversity and coordinated action of Maf family members enable flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115796"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246665","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

RNA m⁶A dynamics promote transcription and RNA stability of bivalent genes during iPSC-induced generation of human lung progenitors. 在ipsc诱导的人肺祖细胞生成过程中，RNA m6A动态促进了二价基因的转录和RNA稳定性。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-06 DOI: 10.1016/j.celrep.2025.115802

Shenghua Dong, Junjie Pang, Yushuai Wang, Le Han, Xiaoxiao Zhou, Feng Huang, Subo Zhang, Ning Ma, Huilin Huang, Hengyou Weng

{"title":"RNA m6A dynamics promote transcription and RNA stability of bivalent genes during iPSC-induced generation of human lung progenitors.","authors":"Shenghua Dong, Junjie Pang, Yushuai Wang, Le Han, Xiaoxiao Zhou, Feng Huang, Subo Zhang, Ning Ma, Huilin Huang, Hengyou Weng","doi":"10.1016/j.celrep.2025.115802","DOIUrl":"10.1016/j.celrep.2025.115802","url":null,"abstract":"RNA N6-methyladenosine (m6A) modifications play a crucial role in the control of RNA synthesis and metabolism during embryonic development. However, the m6A landscape and its impact on early embryonic lung development remain elusive. In this study, we uncover the dynamic and stage-specific patterns of the m6A methylome that correlate with gene expression changes during the differentiation of human induced pluripotent stem cells (iPSCs) into lung progenitors (LPs). Mechanistically, RNA binding motif protein 15B (RBM15B) is upregulated and enhances m6A modification in differentiated cells. Concurrently, the loss of the m6A reader YTH domain-containing protein 1 (YTHDC1) alleviates Polycomb repressive complex 2 (PRC2)-mediated transcriptional silencing of bivalent genes such as GATA4, GATA6, and EOMES. Moreover, the upregulation of another m6A reader, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), further stabilizes these messenger RNA (mRNA) transcripts. The switch of m6A readers coordinates chromatin remodeling and post-transcriptional regulation to drive lung endoderm specification. This study highlights the delicate m6A-centered regulatory mechanisms and the indispensable role of m6A modification in the early stages of embryonic lung development.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115802"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246673","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

Physiological role and mechanisms of action for a long noncoding haplotype region. 长非编码单倍型区域的生理作用和作用机制。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-09 DOI: 10.1016/j.celrep.2025.115805

Hong Xue, Manoj K Mishra, Yong Liu, Pengyuan Liu, Michael Grzybowski, Rajan Pandey, Kristie Usa, Mark A Vanden Avond, Niharika Bala, Abdel A Alli, Allen W Cowley, Qiongzi Qiu, Andrew S Greene, Sridhar Rao, Caitlin C O'Meara, Aron M Geurts, Mingyu Liang

{"title":"Physiological role and mechanisms of action for a long noncoding haplotype region.","authors":"Hong Xue, Manoj K Mishra, Yong Liu, Pengyuan Liu, Michael Grzybowski, Rajan Pandey, Kristie Usa, Mark A Vanden Avond, Niharika Bala, Abdel A Alli, Allen W Cowley, Qiongzi Qiu, Andrew S Greene, Sridhar Rao, Caitlin C O'Meara, Aron M Geurts, Mingyu Liang","doi":"10.1016/j.celrep.2025.115805","DOIUrl":"10.1016/j.celrep.2025.115805","url":null,"abstract":"Direct targeting of noncoding genomic regions harboring common sequence variants associated with human traits through in vivo animal model studies and precise genome editing in human cells is essential for closing the critical gap between genetic discoveries and physiological understanding. However, such investigation has been impractical for many of these variants as they are in haplotypes containing multiple single-nucleotide polymorphisms (SNPs) spanning thousands of base pairs and have small effect sizes. We developed an integrated approach to address this challenge, combining an efficient two-step technique to precisely edit large haplotypes in human induced pluripotent stem cells and orthologous region deletion in phenotypically permissive animal models. As proof of principle, we applied this approach to examine a blood pressure-associated locus with a noncoding haplotype containing 11 SNPs spanning 17.4 kbp. We found a robust blood pressure effect of nearly 10 mmHg and identified the physiological and molecular mechanisms involved.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115805"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265439","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

Yeast TIA1 coordinates with Npl3 to promote ATG1 translation during starvation. 酵母TIA1与Npl3协同促进饥饿期间ATG1的翻译。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-11 DOI: 10.1016/j.celrep.2025.115847

Shree Padma Metur, Xinxin Song, Sophie Mehta, Dimitra Dialynaki, Dibyendu Bhattacharyya, Zhangyuan Yin, Daolin Tang, Daniel J Klionsky

引用次数: 0

Modulation of motor excitability reflects traveling waves of neural oscillations. 运动兴奋性的调节反映了神经振荡的行波。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-14 DOI: 10.1016/j.celrep.2025.115864

Zachary J Haigh, Harry Tran, Taylor Berger, Sina Shirinpour, Ivan Alekseichuk, Seth Koenig, Jan Zimmermann, Robert McGovern, David Darrow, Alexander Herman, Miles Wischnewski, Alexander Opitz

{"title":"Modulation of motor excitability reflects traveling waves of neural oscillations.","authors":"Zachary J Haigh, Harry Tran, Taylor Berger, Sina Shirinpour, Ivan Alekseichuk, Seth Koenig, Jan Zimmermann, Robert McGovern, David Darrow, Alexander Herman, Miles Wischnewski, Alexander Opitz","doi":"10.1016/j.celrep.2025.115864","DOIUrl":"10.1016/j.celrep.2025.115864","url":null,"abstract":"Neural traveling waves represent an important endogenous phenomenon with structural and functional relevance in the human brain. These waves, commonly recorded via electroencephalogram (EEG) or electrocorticography (ECoG), are implicated in a range of brain processes. However, it remains unclear how they influence neural excitability across brain regions. Advancements in real-time control of brain stimulation present opportunities to compare traveling waves and excitation. Here, we investigate how sensorimotor mu (8-13 Hz) and beta (14-30 Hz) traveling waves affect motor cortex excitability using real-time EEG-controlled transcranial magnetic stimulation (TMS). We observed gradients in the mediolateral direction and then validated these findings using ECoG recordings in a human participant and a nonhuman primate. Our results demonstrate that neuronal excitability reflects the natural patterns of sensorimotor traveling waves. This provides important evidence of traveling waves modulating neural excitability in humans. This opens possibilities for more effective stimulation protocols aligned with intrinsic brain dynamics.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115864"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301196","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 mouse posterior insular cortex encodes expressive and receptive aspects of courtship vocalizations. 老鼠的后岛叶皮层编码求偶声音的表达和接受方面。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-06-14 DOI: 10.1016/j.celrep.2025.115850

Thomas Pomberger, Katherine S Kaplan, Rene Carter, Autumn Wetsel, Thomas C Harmon, Richard Mooney

引用次数: 0

Glycerophospholipid metabolism licenses IgE-mediated mast cell degranulation. 甘油磷脂代谢允许ige介导的肥大细胞脱颗粒。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-20 DOI: 10.1016/j.celrep.2025.115742

Yaoyao Xia, Peng Bin, Youyou Zhou, Muyang Zhao, Jianglin Zhang, Weiming Zhong, Na Wang, Bingfeng Wang, Wenkai Ren

{"title":"Glycerophospholipid metabolism licenses IgE-mediated mast cell degranulation.","authors":"Yaoyao Xia, Peng Bin, Youyou Zhou, Muyang Zhao, Jianglin Zhang, Weiming Zhong, Na Wang, Bingfeng Wang, Wenkai Ren","doi":"10.1016/j.celrep.2025.115742","DOIUrl":"10.1016/j.celrep.2025.115742","url":null,"abstract":"Immunoglobulin E (IgE) antibodies and mast cells have been extensively recognized to dictate the pathophysiology of anaphylaxis and allergic reactions; nevertheless, the pivotal cues driving IgE-mediated mast cell degranulation remain enigmatic. Here, we demonstrate that FcεRI aggregation-initiated p38α signaling stimulates Ets-1 transcription by recruitment of the SWI-SNF chromatin-remodeling complex, contributing to Pcyt1a expression and glycerophospholipid metabolism in IgE-stimulated mast cells. Most importantly, Pcyt1a-mediated glycerophospholipid metabolism facilitates mast cell degranulation through the limited macropinocytosis of FcεRI via altering H3K9me3 deposition at the promoter of Prkcd. Moreover, the metabolic cue functions as an instigator of allergic diseases (e.g., atopic dermatitis [AD]) according to preclinical findings of murine models, in silico analysis of human disease studies, and examination of clinical samples. In summary, our study establishes that lipid metabolism and signaling orchestrate mast cell activation and provides promising therapeutic targets for clinically tackling allergic diseases.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115742"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118951","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

KSHV miRNAs target STING to evade innate immunity and facilitate KSHV lytic reactivation from latency. KSHV miRNAs靶向STING逃避先天免疫，促进KSHV从潜伏期裂解再激活。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-24 DOI: 10.1016/j.celrep.2025.115741

Kimberly Paulsen, Rosenna Chan, Lauren Gay, Zhe Ma

引用次数: 0

Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function. 在器官间串扰中探索脂肪组织来源的细胞外囊泡：对代谢调节和脂肪组织功能的影响。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-22 DOI: 10.1016/j.celrep.2025.115732

Soazig Le Lay, Philipp E Scherer

引用次数: 0

Designed miniproteins potently inhibit and protect against MERS-CoV. 设计的微小蛋白有效抑制和保护MERS-CoV。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-31 DOI: 10.1016/j.celrep.2025.115760

Robert J Ragotte, M Alejandra Tortorici, Nicholas J Catanzaro, Amin Addetia, Brian Coventry, Heather M Froggatt, Jimin Lee, Cameron Stewart, Jack T Brown, Inna Goreshnik, Jeremiah N Sims, Lukas F Milles, Basile I M Wicky, Matthias Glögl, Stacey Gerben, Alex Kang, Asim K Bera, William Sharkey, Alexandra Schäfer, Jack R Harkema, Ralph S Baric, David Baker, David Veesler

{"title":"Designed miniproteins potently inhibit and protect against MERS-CoV.","authors":"Robert J Ragotte, M Alejandra Tortorici, Nicholas J Catanzaro, Amin Addetia, Brian Coventry, Heather M Froggatt, Jimin Lee, Cameron Stewart, Jack T Brown, Inna Goreshnik, Jeremiah N Sims, Lukas F Milles, Basile I M Wicky, Matthias Glögl, Stacey Gerben, Alex Kang, Asim K Bera, William Sharkey, Alexandra Schäfer, Jack R Harkema, Ralph S Baric, David Baker, David Veesler","doi":"10.1016/j.celrep.2025.115760","DOIUrl":"10.1016/j.celrep.2025.115760","url":null,"abstract":"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins that bind with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the dipeptidylpeptidase 4 (DPP4) receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice, motivating its future clinical development as a next-generation countermeasure against this virus with pandemic potential.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 6","pages":"115760"},"PeriodicalIF":7.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198343","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