Genes to Cells最新文献_第7页

HIF1α Plays a Crucial Role in the Development of TFE3–Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis HIF1α通过协调向脂肪酸合成的代谢转变在tfe3重排肾细胞癌的发展中起关键作用。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-01-14 DOI: 10.1111/gtc.13195

Hidekazu Nishizawa, Shintaro Funasaki, Wenjuan Ma, Yoshiaki Kubota, Kazuhide Watanabe, Yuichiro Arima, Shoichiro Kuroda, Takaaki Ito, Mitsuko Furuya, Takanobu Motoshima, Akira Nishiyama, Sally Mehanna, Yorifumi Satou, Hisashi Hasumi, Ryosuke Jikuya, Kazuhide Makiyama, Tomohiko Tamura, Yuichi Oike, Yasuhito Tanaka, Toshio Suda, Laura S. Schmidt, W. Marston Linehan, Masaya Baba, Tomomi Kamba

{"title":"HIF1α Plays a Crucial Role in the Development of TFE3–Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis","authors":"Hidekazu Nishizawa, Shintaro Funasaki, Wenjuan Ma, Yoshiaki Kubota, Kazuhide Watanabe, Yuichiro Arima, Shoichiro Kuroda, Takaaki Ito, Mitsuko Furuya, Takanobu Motoshima, Akira Nishiyama, Sally Mehanna, Yorifumi Satou, Hisashi Hasumi, Ryosuke Jikuya, Kazuhide Makiyama, Tomohiko Tamura, Yuichi Oike, Yasuhito Tanaka, Toshio Suda, Laura S. Schmidt, W. Marston Linehan, Masaya Baba, Tomomi Kamba","doi":"10.1111/gtc.13195","DOIUrl":"10.1111/gtc.13195","url":null,"abstract":"Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3–rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α. The upregulation of HIF1α by PRCC-TFE3 led to increased cellular ATP production by enhancing glycolysis, which also supplied substrates for the TCA cycle while maintaining mitochondrial oxidative phosphorylation. We crossed TFE3-RCC mouse models with Hif1α and/or Hif2α knockout mice and found that Hif1α, rather than Hif2α, is essential for tumor development in vivo. RNA-seq and metabolomic analyses of the kidney tissues from these mice revealed that ketone body production is inversely correlated with tumor development, whereas de novo lipid synthesis is upregulated through the HIF1α/SREBP1-dependent mechanism in TFE3-RCC. Our data suggest that the coordinated metabolic shift via the PRCC-TFE3/HIF1α/SREBP1 axis is a key mechanism by which PRCC-TFE3 enhances cancer cell metabolism, promoting tumor development in TFE3-RCC.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Single-Cell RNA-Sequencing of Zebrafish Olfactory Epithelium Identifies Odor-Responsive Candidate Olfactory Receptors 斑马鱼嗅觉上皮单细胞rna测序鉴定气味反应候选嗅觉受体。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-01-09 DOI: 10.1111/gtc.13191

Misaki Takaoka, Towako Hiraki-Kajiyama, Nobuhiko Miyasaka, Takahiro Hino, Kenji Kondo, Yoshihiro Yoshihara

{"title":"Single-Cell RNA-Sequencing of Zebrafish Olfactory Epithelium Identifies Odor-Responsive Candidate Olfactory Receptors","authors":"Misaki Takaoka, Towako Hiraki-Kajiyama, Nobuhiko Miyasaka, Takahiro Hino, Kenji Kondo, Yoshihiro Yoshihara","doi":"10.1111/gtc.13191","DOIUrl":"10.1111/gtc.13191","url":null,"abstract":"Single-cell RNA-sequencing (scRNA-seq) is a powerful method to comprehensively overlook gene expression profiles of individual cells in various tissues, providing fundamental datasets for classification of cell types and further functional analyses. Here we adopted scRNA-seq analysis for the zebrafish olfactory sensory neurons which respond to water-borne odorants and pheromones to elicit various behaviors crucial for survival and species preservation. Firstly, a single-cell dissociation procedure of the zebrafish olfactory rosettes was optimized by using cold-active protease, minimizing artifactual neuronal activation. Secondly, various cell types were classified into distinct clusters, based on the expressions of well-defined marker genes. Notably, we validated non-overlapping expressions of different families of olfactory receptors among the clusters of olfactory sensory neurons. Lastly, we succeeded in estimating candidate olfactory receptors responding to a particular odor stimulus by carefully scrutinizing correlated expressions of immediate early genes. Thus, scRNA-seq is a useful measure for the analysis of olfactory sensory neurons not only in classifying functional cell types but also in identifying olfactory receptor genes for given odorants and pheromones.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

SRPKs Homolog Dsk1 Regulates Homologous Recombination Repair in Schizosaccharomyces pombe SRPKs同源Dsk1调控裂糖酵母同源重组修复。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-01-09 DOI: 10.1111/gtc.13192

Guangchun Lu, Zhiheng Tang, Mei Wu, Li Liu, Mitchell Opoku, Kaicheng Bian, Rui Ruan, Jinjie Shang, Jia Liu, Gang Feng

{"title":"SRPKs Homolog Dsk1 Regulates Homologous Recombination Repair in Schizosaccharomyces pombe","authors":"Guangchun Lu, Zhiheng Tang, Mei Wu, Li Liu, Mitchell Opoku, Kaicheng Bian, Rui Ruan, Jinjie Shang, Jia Liu, Gang Feng","doi":"10.1111/gtc.13192","DOIUrl":"10.1111/gtc.13192","url":null,"abstract":"<div>\u0000 \u0000 Serine-arginine protein kinases (SRPKs) play important roles in diverse biological processes such as alternative splicing and cell cycle. However, the functions of SRPKs in DNA damage response remain unclear. Here we characterized the function of SRPKs homolog Dsk1 in regulating DNA repair in the fission yeast Schizosaccharomyces pombe. We demonstrated that Dsk1 defective mutants of loss of the gene, spacer domain, and kinase activity as well as its overexpression mutant exhibited sensitivities of replication stress. Genetic analysis revealed that the loss of dsk1+ compromised the efficiency of homologous recombination (HR) repair, and Dsk1 was probably involved in the Rad52- and Rad51-dependent HR repair pathways. Interestingly, Dsk1 translocated into the nucleus upon replication stress and directly interacted with Rad51-mediator Rad52 and phosphorylated Rad52-Ser365 residue. The Rad52-Ser365 phosphorylation-defective mutant was slightly sensitive to replication stress, and the phosphorylation-mimicking mutants exhibited more sensitivities, which were partially correlated with phenotypes of the loss- and gain-of-function of dsk1+. This study uncovers a potential HR repair regulator Dsk1 in response to replication stress and implies that its homolog SRPKs may have the conserved targets and functions in higher eukaryotes.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Swimming Into Future Breakthroughs From Kyoto, Japan: Report of the 18th International Zebrafish Conference (IZFC2024) 从日本京都游向未来的突破：第18届国际斑马鱼会议（IZFC2024）报告。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-01-07 DOI: 10.1111/gtc.13193

Hiromi Hirata, Tohru Ishitani, Hitoshi Okamoto

{"title":"Swimming Into Future Breakthroughs From Kyoto, Japan: Report of the 18th International Zebrafish Conference (IZFC2024)","authors":"Hiromi Hirata, Tohru Ishitani, Hitoshi Okamoto","doi":"10.1111/gtc.13193","DOIUrl":"10.1111/gtc.13193","url":null,"abstract":"<div>\u0000 \u0000 The 18th International Zebrafish Conference (IZFC2024) took place from August 17 to 21, 2024, at Miyako Messe in Kyoto, Japan. This conference attracted 641 researchers from around the world along with 83 virtual participants, making it the largest gathering since the COVID-19 pandemic. The event featured two keynote lectures, three award lectures, 36 plenary talks, 90 oral presentations, and 374 poster presentations. Participants also engaged in luncheons, workshops, and community sessions, all aimed at exploring innovative technologies, enhancing scientific environments and strengthening connections within the research community. Additionally, the conference included cultural elements that allowed participants to immerse themselves in Japanese traditions, enriching their overall experience. This commitment to blending scientific inquiry with cultural appreciation ensured that participants gained valuable insights into the latest research while enjoying a taste of Japan's rich heritage. Overall, IZFC2024 successfully promoted collaboration and innovation in zebrafish research while celebrating the unique cultural aspects of Japan, making this conference an unforgettable event for everyone involved.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Transition From Interindividual Uniformity to Diversity in Appearance and Transcriptional Features at Midlife in Caenorhabditis elegans 中年秀丽隐杆线虫外貌和转录特征从个体间一致性到多样性的过渡。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2025-01-01 DOI: 10.1111/gtc.13187

Masaharu Uno, Masanori Nono, Chika Takahashi, Saya Kishimoto, Emiko Okabe, Takuya Yamamoto, Eisuke Nishida

{"title":"A Transition From Interindividual Uniformity to Diversity in Appearance and Transcriptional Features at Midlife in Caenorhabditis elegans","authors":"Masaharu Uno, Masanori Nono, Chika Takahashi, Saya Kishimoto, Emiko Okabe, Takuya Yamamoto, Eisuke Nishida","doi":"10.1111/gtc.13187","DOIUrl":"10.1111/gtc.13187","url":null,"abstract":"<div>\u0000 \u0000 During embryogenesis, organisms function as a robust system that ensures uniformity within individuals, but they lose robustness and develop variations at advanced ages. However, when and how organisms lose this robustness remains largely elusive. Here, we identified a sharp transition from interindividual uniformity to diversity in the appearance and transcriptional features of age-matched Caenorhabditis elegans in midlife. Convolutional neural network analysis of individual appearance alterations revealed that the transition occurs in midlife, which coincides with the cessation of egg-laying activity and increased motility defects. This period represents the transition from the young state, marked by shared homogeneous features among same-age individuals, to the old state, marked by shared among old individuals. Transcriptional coherence within the age-matched individuals shows essentially the same transition, coinciding with the appearance features. These findings provide a new framework for understanding the aging trajectory in C. elegans, demonstrating the occurrence of the loss of robust control over appearance and transcriptional homeostasis in midlife.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Sulforaphane Induces Transient Reactive Oxygen Species-Mediated DNA Damage in HeLa Cells 萝卜硫素诱导HeLa细胞瞬时活性氧介导的DNA损伤。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-12-27 DOI: 10.1111/gtc.13190

Sakine Kobayashi, Seiya Nishiba, Chinatsu Sato, Kazuya Toriumi, Yuduki Someya, Noritaka Adachi, Shigeki Takeda, Aya Kurosawa

{"title":"Sulforaphane Induces Transient Reactive Oxygen Species-Mediated DNA Damage in HeLa Cells","authors":"Sakine Kobayashi, Seiya Nishiba, Chinatsu Sato, Kazuya Toriumi, Yuduki Someya, Noritaka Adachi, Shigeki Takeda, Aya Kurosawa","doi":"10.1111/gtc.13190","DOIUrl":"10.1111/gtc.13190","url":null,"abstract":"<div>\u0000 \u0000 Sulforaphane (SFN), an isothiocyanate found in plants of the Brassicaceae family, possesses antioxidant, apoptosis-inducing, and radiosensitizing effects. As one of the mechanisms of cytotoxicity by SFN, SFN has been suggested to be involved in the induction of DNA damage and inhibition of DNA repair. Recently, we reported on the potency of SFN in inducing single-ended double-strand breaks (DSBs) that are caused by the collision of replication forks with single-strand breaks (SSBs). However, the mechanism of SSB accumulation by SFN remains unclear. In this study, we examined the effect of SFN on SSB-inducing factors in HeLa cells. Although the inhibitory effect of SFN on DNA topoisomerase I was not observed, we found that the reduced form of glutathione (GSH; an antioxidant) level was decreased in an SFN concentration-dependent manner. Furthermore, the addition of ascorbic acid partially increased the viability of SFN-treated HeLa cells. We subsequently observed that poly(ADP-ribose) accumulated in SFN-treated HeLa cells, which occurs during early SSB repair. Collectively, these findings suggest that SFN may transiently induce SSBs via reactive oxygen species in HeLa cells.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Identification of Gallbladder-Specific Distal Regulatory Sequence of Murine Sox17 小鼠胆囊特异性Sox17远端调控序列的鉴定。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-12-26 DOI: 10.1111/gtc.13186

Shihan Zeng, Ayaka Yanagida, Noriaki Ota, Mami Uemura, Yoshikazu Hirate, Ryuji Hiramatsu, Naoaki Mizuno, Yoshiakira Kanai, Masami Kanai-Azuma

{"title":"Identification of Gallbladder-Specific Distal Regulatory Sequence of Murine Sox17","authors":"Shihan Zeng, Ayaka Yanagida, Noriaki Ota, Mami Uemura, Yoshikazu Hirate, Ryuji Hiramatsu, Naoaki Mizuno, Yoshiakira Kanai, Masami Kanai-Azuma","doi":"10.1111/gtc.13186","DOIUrl":"10.1111/gtc.13186","url":null,"abstract":"Sox17 is a key transcriptional regulator of endoderm formation and function in the gallbladder, blood vessels and reproductive organs. Although multiple transcript variants of Sox17 have been suggested, the precise mechanisms underlying their time- and tissue-specific expression remain unclear. In this study, we discovered two putative regulatory sequences (R1 and R2) adjacent to different transcription start sites of mouse Sox17 exon 1 and generated deletion mice for these regions (Sox17Δdr/Δdr). Sox17Δdr/Δdr mice were alive and fertile, and they possessed a normal-sized gallbladder. However, semiquantitative analysis of immunostaining showed that the expression levels of SOX17 in Sox17Δdr/Δdr embryos were reduced to less than 50% of the wild-type in the gallbladder epithelium. Furthermore, the bile ductal epithelium marker SOX9 was abnormally upregulated, and PAS/DBA-positive mucin secretion-like epithelial cells were induced in the Sox17Δdr/Δdr gallbladder. Our results demonstrate that the distal sequence of Sox17, including R1 and R2, is important for the regulation of Sox17 gene expression in the embryonic gallbladder and is crucial for normal gallbladder epithelial development.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Interferon-Dependent Expression of the Human STAT1 Gene Requires a Distal Regulatory Region Located Approximately 6 kb Upstream for Its Autoregulatory System 人类STAT1基因的干扰素依赖性表达需要一个位于上游约6kb的远端调控区来实现其自动调控系统。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-12-25 DOI: 10.1111/gtc.13188

Katsutoshi Yuasa, Aimi Masubuchi, Tomo Okada, Miho Shinya, Yui Inomata, Honoka Kida, Sayoko Shyouji, Hirona Ichikawa, Tetsuyuki Takahashi, Masashi Muroi, Takao Hijikata

{"title":"Interferon-Dependent Expression of the Human STAT1 Gene Requires a Distal Regulatory Region Located Approximately 6 kb Upstream for Its Autoregulatory System","authors":"Katsutoshi Yuasa, Aimi Masubuchi, Tomo Okada, Miho Shinya, Yui Inomata, Honoka Kida, Sayoko Shyouji, Hirona Ichikawa, Tetsuyuki Takahashi, Masashi Muroi, Takao Hijikata","doi":"10.1111/gtc.13188","DOIUrl":"10.1111/gtc.13188","url":null,"abstract":"<div>\u0000 \u0000 We previously suggested that the signal transducer and activator of transcription 1 (STAT1) gene is autoregulated in an interferon (IFN)-dependent manner via a distal regulatory region approximately 5.5–6.2 kb upstream of the murine and human STAT1 promoters (designated 5.5URR). Here, we examined whether this IFN-dependent positive feedback mechanism of the STAT1 gene actually functions in cells. First, we created human embryonic kidney 293 cell mutants lacking the IFN-responsive transcription factor binding sites (IFN-stimulated response element and IFN-gamma-activated sequence) within the 5.5URR and stimulated them with IFN-α/γ. The mutants showed a loss of response to IFN, indicating that the 5.5URR is essential for IFN-induced transcriptional enhancement in STAT1 gene expression. Second, we cloned the full-length 11 kb human STAT1 promoter, including the region upstream of the 5.5URR, from the start codon and linked it to a luciferase gene. Reporter assays showed that IFN-α/γ significantly activated the STAT1 promoter via the 5.5URR. Furthermore, recombinant DNA linking the full-length STAT1 promoter to STAT1 cDNA was introduced into STAT1-deficient cells. In vitro reconstitution experiments showed that IFN-α/γ stimulation increased STAT1 protein levels via the 5.5URR. These results demonstrate that the 5.5URR confers IFN-dependent autoregulation of the STAT1 promoter.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Rapamycin Abrogates Aggregation of Human α-Synuclein Expressed in Fission Yeast via an Autophagy-Independent Mechanism 雷帕霉素通过不依赖自噬的机制抑制分裂酵母中表达的人α-突触核蛋白的聚集。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-12-18 DOI: 10.1111/gtc.13185

Yoshitaka Sugimoto, Teruaki Takasaki, Ryuga Yamada, Ryo Kurosaki, Tomonari Yamane, Reiko Sugiura

{"title":"Rapamycin Abrogates Aggregation of Human α-Synuclein Expressed in Fission Yeast via an Autophagy-Independent Mechanism","authors":"Yoshitaka Sugimoto, Teruaki Takasaki, Ryuga Yamada, Ryo Kurosaki, Tomonari Yamane, Reiko Sugiura","doi":"10.1111/gtc.13185","DOIUrl":"10.1111/gtc.13185","url":null,"abstract":"<div>\u0000 \u0000 Aggregation of alpha-synuclein (α-Syn) is implicated in the pathogenesis of several neurodegenerative disorders, such as Parkinson's disease and Dementia with Lewy bodies, collectively termed synucleinopathies. Thus, tremendous efforts are being made to develop strategies to prevent or inhibit α-Syn aggregation. Here, we genetically engineered fission yeast to express human α-Syn C-terminally fused to green fluorescent protein (GFP) at low and high levels. α-Syn was localized at the cell tips and septa at low-level expression. At high-level expression, α-Syn was observed to form cytoplasmic aggregates. Notably, rapamycin, a natural product that allosterically inhibits the mammalian target of rapamycin (mTOR) by forming a complex with FKBP12, and Torin1, a synthetic mTOR inhibitor that blocks ATP binding to mTOR, markedly reduced the number of cells harboring α-Syn aggregates. These mTOR inhibitors abrogate α-Syn aggregation without affecting α-Syn expression levels. Rapamycin, but not Torin1, failed to reduce α-Syn aggregation in the deletion cells of fkh1+, encoding FKBP12, indicating the requirement of FKBP12 for rapamycin-mediated inhibition of α-Syn aggregation. Importantly, the effect of rapamycin was also observed in the cells lacking atg1+, a key regulator of autophagy. Collectively, rapamycin abrogates human α-Syn aggregation expressed in fission yeast via an autophagy-independent mechanism mediated by FKBP12.\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Defects in the H3t Gene Cause an Increase in Leydig Cells With Impaired Spermatogenesis in Mice H3t基因缺陷导致小鼠间质细胞增加，精子发生受损。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-12-03 DOI: 10.1111/gtc.13182

Qianmei Wu, Miho Ito, Takeru Fujii, Kaori Tanaka, Kohta Nakatani, Yoshihiro Izumi, Takeshi Bamba, Takashi Baba, Kazumitsu Maehara, Kosuke Tomimatsu, Tatsuya Takemoto, Yasuyuki Ohkawa, Akihito Harada

{"title":"Defects in the H3t Gene Cause an Increase in Leydig Cells With Impaired Spermatogenesis in Mice","authors":"Qianmei Wu, Miho Ito, Takeru Fujii, Kaori Tanaka, Kohta Nakatani, Yoshihiro Izumi, Takeshi Bamba, Takashi Baba, Kazumitsu Maehara, Kosuke Tomimatsu, Tatsuya Takemoto, Yasuyuki Ohkawa, Akihito Harada","doi":"10.1111/gtc.13182","DOIUrl":"10.1111/gtc.13182","url":null,"abstract":"Abnormalities in spermatogenesis, a fundamental component of male reproductive function, can cause male infertility. Somatic cells constituting the testis microenvironment are essential for controlling normal spermatogenesis. Although testicular somatic cells are thought to sense and respond to germ cells to ensure proper spermatogenesis, the details of this signaling mechanism are unknown. Here, we investigated somatic cell dynamics in testicular tissue lacking spermatogenesis using the mice with deletion of the testis-specific histone H3 variant gene H3t. Testicular tissue sections of H3tΔ/Δ mice exhibited an increased interstitial area compared with those of wild-type mice, which was primarily attributed to an increase in Leydig cell numbers. Furthermore, this increase in Leydig cells led to increased testosterone synthesis, which occurred alongside cellular senescence-associated β-galactosidase activity. These findings suggest that Leydig cells monitor the progress of spermatogenesis and possess a mechanism to promote functional germ cell formation.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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