EMBO Reports最新文献_第10页

Gpr54 deletion accelerates hair cycle and hair regeneration. Gpr54 基因缺失可加速毛发周期和毛发再生。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1038/s44319-024-00327-y

Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang

{"title":"Gpr54 deletion accelerates hair cycle and hair regeneration.","authors":"Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang","doi":"10.1038/s44319-024-00327-y","DOIUrl":"10.1038/s44319-024-00327-y","url":null,"abstract":"GPR54, or KiSS-1R (Kisspeptin receptor), is key in puberty initiation and tumor metastasis prevention, but its role on hair follicles remains unclear. Our study shows that Gpr54 knockout (KO) accelerates hair cycle, synchronized hair regeneration and transplanted hair growth in mice. In Gpr54 KO mice, DPC (dermal papilla cell) activity is enhanced, with elevated expression of Wnts, VEGF, and IGF-1, which stimulate HFSCs. Gpr54 deletion also raises the number of CD34+ and Lgr5+ HFSCs. The Gpr54 inhibitor, kisspeptin234, promotes hair shaft growth in cultured mouse hair follicles and boosts synchronized hair regeneration in vivo. Mechanistically, Gpr54 deletion suppresses NFATC3 expression in DPCs and HFSCs, and decreases levels of SFRP1, a Wnt inhibitor. It also activates the Wnt/β-catenin pathway, promoting β-catenin nuclear localization and upregulating target genes such as Lef1 and ALP. Our findings suggest that Gpr54 deletion may accelerate the hair cycle and promote hair regeneration in mice by regulating the NAFTc3-SFRP1-Wnt signaling pathway. These findings suggest that Gpr54 could be a possible target for future hair loss treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"200-217"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Local translatome sustains synaptic function in impaired Wallerian degeneration. 在沃勒里变性受损的情况下，局部转译体能维持突触功能。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.1038/s44319-024-00301-8

Maria Paglione, Leonardo Restivo, Sarah Zakhia, Arnau Llobet Rosell, Marco Terenzio, Lukas J Neukomm

{"title":"Local translatome sustains synaptic function in impaired Wallerian degeneration.","authors":"Maria Paglione, Leonardo Restivo, Sarah Zakhia, Arnau Llobet Rosell, Marco Terenzio, Lukas J Neukomm","doi":"10.1038/s44319-024-00301-8","DOIUrl":"10.1038/s44319-024-00301-8","url":null,"abstract":"After injury, severed axons separated from their somas activate programmed axon degeneration, a conserved pathway to initiate their degeneration within a day. Conversely, severed projections deficient in programmed axon degeneration remain morphologically preserved with functional synapses for weeks to months after axotomy. How this synaptic function is sustained remains currently unknown. Here, we show that dNmnat overexpression attenuates programmed axon degeneration in distinct neuronal populations. Severed projections remain morphologically preserved for weeks. When evoked, they elicit a postsynaptic behavior, a readout for preserved synaptic function. We used ribosomal pulldown to isolate the translatome from these projections 1 week after axotomy. Translatome candidates of enriched biological classes identified by transcriptional profiling are validated in a screen using a novel automated system to detect evoked antennal grooming as a proxy for preserved synaptic function. RNAi-mediated knockdown reveals that transcripts of the mTORC1 pathway, a mediator of protein synthesis, and of candidate genes involved in protein ubiquitination and Ca2+ homeostasis are required for preserved synaptic function. Our translatome dataset also uncovers several uncharacterized Drosophila genes associated with human disease. It may offer insights into novel avenues for therapeutic treatments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"61-83"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BBSome-deficient cells activate intraciliary CDC42 to trigger actin-dependent ciliary ectocytosis. BBSome 缺陷细胞激活睫状体内 CDC42，触发肌动蛋白依赖性睫状体外吞。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1038/s44319-024-00326-z

Avishek Prasai, Olha Ivashchenko, Kristyna Maskova, Sofiia Bykova, Marketa Schmidt Cernohorska, Ondrej Stepanek, Martina Huranova

{"title":"BBSome-deficient cells activate intraciliary CDC42 to trigger actin-dependent ciliary ectocytosis.","authors":"Avishek Prasai, Olha Ivashchenko, Kristyna Maskova, Sofiia Bykova, Marketa Schmidt Cernohorska, Ondrej Stepanek, Martina Huranova","doi":"10.1038/s44319-024-00326-z","DOIUrl":"10.1038/s44319-024-00326-z","url":null,"abstract":"Bardet-Biedl syndrome (BBS) is a pleiotropic ciliopathy caused by dysfunction of the BBSome, a cargo adaptor essential for export of transmembrane receptors from cilia. Although actin-dependent ectocytosis has been proposed to compensate defective cargo retrieval, its molecular basis remains unclear, especially in relation to BBS pathology. In this study, we investigated how actin polymerization and ectocytosis are regulated within the cilium. Our findings reveal that ciliary CDC42, a RHO-family GTPase triggers in situ actin polymerization, ciliary ectocytosis, and cilia shortening in BBSome-deficient cells. Activation of the Sonic Hedgehog pathway further enhances CDC42 activity specifically in BBSome-deficient cilia. Inhibition of CDC42 in BBSome-deficient cells decreases the frequency and duration of ciliary actin polymerization events, causing buildup of G protein coupled receptor 161 (GPR161) in bulges along the axoneme during Sonic Hedgehog signaling. Overall, our study identifies CDC42 as a key trigger of ciliary ectocytosis. Hyperactive ciliary CDC42 and ectocytosis and the resulting loss of ciliary material might contribute to BBS disease severity.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"36-60"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The trap of a closed fist : Is democracy capable of preventing a global ecological catastrophe? 握紧拳头的陷阱：民主能够防止全球生态灾难吗？

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI: 10.1038/s44319-024-00341-0

Vladimir Leksa

引用次数: 0

Experience-driven development of decision-related representations in the auditory cortex. 听觉皮层中决策相关表征的经验驱动发展。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-11 DOI: 10.1038/s44319-024-00309-0

Itay Kazanovich, Shir Itzhak, Jennifer Resnik

{"title":"Experience-driven development of decision-related representations in the auditory cortex.","authors":"Itay Kazanovich, Shir Itzhak, Jennifer Resnik","doi":"10.1038/s44319-024-00309-0","DOIUrl":"10.1038/s44319-024-00309-0","url":null,"abstract":"Associating sensory stimuli with behavioral significance induces substantial changes in stimulus representations. Recent studies suggest that primary sensory cortices not only adjust representations of task-relevant stimuli, but actively participate in encoding features of the decision-making process. We sought to determine whether this trait is innate in sensory cortices or if choice representation develops with time and experience. To trace choice representation development, we perform chronic two-photon calcium imaging in the primary auditory cortex of head-fixed mice while they gain experience in a tone detection task with a delayed decision window. Our results reveal a progressive increase in choice-dependent activity within a specific subpopulation of neurons, aligning with growing task familiarity and adapting to changing task rules. Furthermore, task experience correlates with heightened synchronized activity in these populations and the ability to differentiate between different types of behavioral decisions. Notably, the activity of this subpopulation accurately decodes the same action at different task phases. Our findings establish a dynamic restructuring of population activity in the auditory cortex to encode features of the decision-making process that develop over time and refines with experience.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"84-100"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transposable element activity captures human pluripotent cell states. 转座因子活性捕获人类多能细胞状态。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI: 10.1038/s44319-024-00343-y

Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano

{"title":"Transposable element activity captures human pluripotent cell states.","authors":"Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano","doi":"10.1038/s44319-024-00343-y","DOIUrl":"10.1038/s44319-024-00343-y","url":null,"abstract":"Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency states compared to conventional systems. Unexpectedly, we identified a rare, metastable cell population within primed hPSCs, marked by transcripts related to preimplantation embryo development and which is associated with a DNA damage response. Moreover, our system establishes the chromatin factor NSD1 and the RNA-binding protein FUS as potent molecular safeguards of primed pluripotency. Our study introduces a novel system for investigating cellular potency and provides key insights into the regulation of embryonic development.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"329-352"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The relevance of the history of biotechnology for healthcare : Teaching students how biotechnology and medicine have been closely entwined during the past century highlights how both fields have inspired and driven each other. 医疗保健生物技术历史的相关性：教授学生生物技术和医学如何在过去的一个世纪里紧密地交织在一起，突出了这两个领域是如何相互启发和推动的。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2025-01-02 DOI: 10.1038/s44319-024-00355-8

Maurizio Bifulco, Erika Di Zazzo, Alessandra Affinito, Cristina Pagano

引用次数: 0

What's in our bin? : Labs kick off and demand the transition towards a circular economy for lab plastics. 我们的垃圾桶里有什么？：实验室启动并要求向实验室塑料循环经济转型。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2025-01-06 DOI: 10.1038/s44319-024-00360-x

Philipp M Weber, Cleophea Michelsen, Melina Kerou

引用次数: 0

Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring. 新颖的多组学综合分析揭示了整合素 beta 样 1 在伤口瘢痕形成中的关键作用。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1038/s44319-024-00322-3

Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori

{"title":"Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring.","authors":"Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori","doi":"10.1038/s44319-024-00322-3","DOIUrl":"10.1038/s44319-024-00322-3","url":null,"abstract":"Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process. Data from PU.1-/- mice, which lack an inflammatory response, combined with scRNA-Seq and Visium transcriptomics, led to the identification of nine genes potentially involved in inflammation-related scarring, including integrin beta-like 1 (Itgbl1). Transgenic mouse experiments confirmed that Itgbl1-expressing fibroblasts are required for granulation tissue formation and drive fibrogenesis during skin repair. Additionally, we detected a minority population of Acta2high-expressing myofibroblasts with apparent involvement in scarring, in conjunction with Itgbl1 expression. IL1β signaling inhibited Itgbl1 expression in TGFβ1-treated primary fibroblasts from humans and mice. Our novel methodology reveal molecular mechanisms underlying fibroblast-inflammatory cell interactions that initiate wound scarring.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"122-152"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterochromatin-dependent transcription links the PRC2 complex to small RNA-mediated DNA elimination. 异染色质依赖性转录将PRC2复合体与小rna介导的DNA消除联系起来。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1038/s44319-024-00332-1

Therese Solberg, Chundi Wang, Ryuma Matsubara, Zhiwei Wen, Mariusz Nowacki

{"title":"Heterochromatin-dependent transcription links the PRC2 complex to small RNA-mediated DNA elimination.","authors":"Therese Solberg, Chundi Wang, Ryuma Matsubara, Zhiwei Wen, Mariusz Nowacki","doi":"10.1038/s44319-024-00332-1","DOIUrl":"10.1038/s44319-024-00332-1","url":null,"abstract":"Facultative heterochromatin is marked by the repressive histone modification H3K27me3 in eukaryotes. Deposited by the PRC2 complex, H3K27me3 is essential for regulating gene expression during development, and chromatin bearing this mark is generally considered transcriptionally inert. The PRC2 complex has also been linked to programmed DNA elimination during development in ciliates such as Paramecium. Due to a lack of mechanistic insight, a direct involvement has been questioned as most eliminated DNA segments in Paramecium are shorter than the size of a nucleosome. Here, we identify two sets of histone methylation readers essential for PRC2-mediated DNA elimination in Paramecium: Firefly1/2 and Mayfly1-4. The chromodomain proteins Firefly1/2 act in tight association with TFIIS4, a transcription elongation factor required for noncoding RNA transcription. These noncoding transcripts act as scaffolds for sequence-specific targeting by PIWI-bound sRNAs, resulting in local nucleosome depletion and DNA elimination. Our findings elucidate the molecular mechanism underlying the role of PRC2 in PIWI-mediated DNA elimination and suggest that its role in IES elimination may be to activate rather than repress transcription.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"273-296"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0