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Image Analysis Characterizes Phenotypic Variation in the Growth of Mushroom-Forming Fungus Schizophyllum commune 图像分析揭示了形成蘑菇的真菌 Schizophyllum commune 生长过程中的表型差异。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-11-26 DOI: 10.1111/gtc.13181
Hiromi Matsumae, Megumi Sudo, Tadashi Imanishi, Tsuyoshi Hosoya
{"title":"Image Analysis Characterizes Phenotypic Variation in the Growth of Mushroom-Forming Fungus Schizophyllum commune","authors":"Hiromi Matsumae,&nbsp;Megumi Sudo,&nbsp;Tadashi Imanishi,&nbsp;Tsuyoshi Hosoya","doi":"10.1111/gtc.13181","DOIUrl":"10.1111/gtc.13181","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Schizophyllum commune</i>, a common wood-decay mushroom known for its extremely high genetic variation and as a rare cause of human respiratory diseases, could be a promising model fungus contributing to both biology and medicine. To better understand its phenotypic variation, we developed an image analysis system that quantifies morphological and physiological traits of mycelial colonies in Petri dishes. This study evaluated growth of six wild and one clinical isolates of Japanese <i>S. commune</i>, subjected to different temperatures and glucose concentrations, including a condition mimicking the human respiratory environment. Our analysis revealed that combinations of two growth indices, area and whiteness, and profiling by clustering algorithms highlighted strain-specific responses. For example, the clinical isolate was the whitest under the respiratory-like condition. We also found that the growth rate was strongly determined by glucose concentration, while the effects of temperature on growth varied among the strains, suggesting that while glucose preference is common in this species, responses to temperature differ between strains. This system showed sufficient sensitivity to detect variation in mycelial growth. Our study provides a key to unraveling morphological and physiological traits behind the high polymorphisms in <i>S. commune</i>, including the ability to colonize the human respiratory tract.</p>\u0000 </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716000","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
Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9-Mediated Interstitial Megabase Deletion 通过 CRISPR/Cas9 介导的间质巨碱基缺失法生成 21q 单体人 iPS 细胞。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-11-24 DOI: 10.1111/gtc.13184
Masaya Egawa, Narumi Uno, Rina Komazaki, Yusuke Ohkame, Kyotaro Yamazaki, Chihiro Yoshimatsu, Yuki Ishizu, Yusaku Okano, Hitomaru Miyamoto, Mitsuhiko Osaki, Teruhiko Suzuki, Kazuyoshi Hosomichi, Yasunori Aizawa, Yasuhiro Kazuki, Kazuma Tomizuka
{"title":"Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9-Mediated Interstitial Megabase Deletion","authors":"Masaya Egawa,&nbsp;Narumi Uno,&nbsp;Rina Komazaki,&nbsp;Yusuke Ohkame,&nbsp;Kyotaro Yamazaki,&nbsp;Chihiro Yoshimatsu,&nbsp;Yuki Ishizu,&nbsp;Yusaku Okano,&nbsp;Hitomaru Miyamoto,&nbsp;Mitsuhiko Osaki,&nbsp;Teruhiko Suzuki,&nbsp;Kazuyoshi Hosomichi,&nbsp;Yasunori Aizawa,&nbsp;Yasuhiro Kazuki,&nbsp;Kazuma Tomizuka","doi":"10.1111/gtc.13184","DOIUrl":"10.1111/gtc.13184","url":null,"abstract":"<p>Missing an entire chromosome or chromosome arm in normal diploid cells has a deleterious impact on cell viability, which may contribute to the development of specific birth defects. Nevertheless, the effects of chromosome loss in human cells have remained unexplored due to the lack of suitable model systems. Here, we developed an efficient, selection-free approach to generate partial monosomy in human induced pluripotent stem cells (iPSCs). The introduction of Cas9 proteins and a pair of gRNAs induces over megabase-sized interstitial chromosomal deletions. Using human chromosome 21 (HSA21) as a model, partial monosomy 21q (PM21q) iPSC lines with deletions ranging from 4.5 to 27.9 Mb were isolated. A 33.6 Mb deletion, encompassing all protein-coding genes on 21q, was also achieved, establishing the first 21q monosomy human iPSC line. Transcriptome and proteome analyses revealed that the abundances of mRNA and protein encoded by the majority of genes in the monosomic regions are half of the diploid expression level, indicating an absence of dosage compensation. The ability to generate customized partial monosomy cell lines on an isogenic, karyotypically normal background should facilitate the gain of novel insights into the impact of chromosome loss on cellular fitness.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709921","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
Chromosomal rearrangements associated with SMC5/6 deficiency in DNA replication 与 DNA 复制中 SMC5/6 缺乏有关的染色体重排。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-11-14 DOI: 10.1111/gtc.13180
Yoshiharu Kusano, Yasuha Kinugasa, Satoshi Tashiro, Toru Hirota
{"title":"Chromosomal rearrangements associated with SMC5/6 deficiency in DNA replication","authors":"Yoshiharu Kusano,&nbsp;Yasuha Kinugasa,&nbsp;Satoshi Tashiro,&nbsp;Toru Hirota","doi":"10.1111/gtc.13180","DOIUrl":"10.1111/gtc.13180","url":null,"abstract":"<p>Completion of DNA replication before chromosome segregation is essential for the stable maintenance of the genome. Under replication stress, DNA synthesis may persist beyond S phase, especially in genomic regions that are difficult to proceed with the replication processes. Incomplete replication in mitosis emerges as non-disjoined segment in mitotic chromosomes leading to anaphase bridges. The resulting chromosome rearrangements are not well characterized, however. Here, we report that incomplete replication due to SMC5/6 deficiency impairs sister chromatid disjunction at difficult-to-replicate regions, including common fragile sites. These non-disjoined regions manifest as cytologically defined symmetric gaps, causing anaphase bridges. These bridges break at the gaps, leading to telomere loss, micronucleation, and fragmentation. Subsequently, fusions between telomere-deficient chromosomes generate complex chromosomal rearrangements, including dicentric chromosomes, suggesting the occurrence of breakage-fusion-bridge cycle. Additionally, chromosomes in micronuclei were pulverized, indicative of chromothripsis. Our findings suggest that incomplete replication facilitates complex chromosomal rearrangements, which may contribute to genomic instability in human cancers.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1251-1263"},"PeriodicalIF":1.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618665","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
The fly brain lands in Tokyo: A report on the 3rd Asia Pacific Drosophila Neurobiology Conference 蝇脑登陆东京:第三届亚太果蝇神经生物学会议报告。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-11-05 DOI: 10.1111/gtc.13178
Gaurav Das, Olfat A. Malak, Khushboo Sharma, Abdalla G. Alia, Swetha Gopalakrishnan, Reshma V. Menon, Hayato M. Yamanouchi, Akinao Nose, Hokto Kazama, Adrian W. Moore, Takashi Suzuki
{"title":"The fly brain lands in Tokyo: A report on the 3rd Asia Pacific Drosophila Neurobiology Conference","authors":"Gaurav Das,&nbsp;Olfat A. Malak,&nbsp;Khushboo Sharma,&nbsp;Abdalla G. Alia,&nbsp;Swetha Gopalakrishnan,&nbsp;Reshma V. Menon,&nbsp;Hayato M. Yamanouchi,&nbsp;Akinao Nose,&nbsp;Hokto Kazama,&nbsp;Adrian W. Moore,&nbsp;Takashi Suzuki","doi":"10.1111/gtc.13178","DOIUrl":"10.1111/gtc.13178","url":null,"abstract":"<p>The third Asia Pacific <i>Drosophila</i> Neurobiology Conference (APDNC3) was held in the Wako Campus of RIKEN in Tokyo, Japan, from February 27th to March 1st, 2024. While APDNC2 was held in Taiwan in 2019, the global coronavirus pandemic enforced a long hiatus. Hence, APDNC3 was a much-anticipated meeting that attracted ~218 scientists from 18 different countries and regions, 154 from outside Japan. The meeting was divided into 13 scientific, 2 poster, and 3 career development sessions. Two plenary talks were delivered by Professor Daisuke Yamamoto, from NICT and Professor Claude Desplan from NYU. Thirty-seven other speakers were invited to give lectures. Eighty-six poster presenters were selected from submitted abstracts. Talks and posters described how neuronal circuits underlying specific behaviors were identified and how they developed. The presented work also demonstrated circuit-specific cellular and molecular mechanisms in health and disease. It was clear that technological advances, like molecular genetic tools for identifying, manipulating, and imaging individual neurons and the great granularity of the fly brain connectome, were significantly augmenting research. Overall, the meeting highlighted the remarkable biological insights that fly neurobiologists continue to provide.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1111-1117"},"PeriodicalIF":1.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582847","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
Immunotherapy-induced reprogramming of cancer-associated fibroblasts can promote tumor progression 免疫疗法诱导的癌症相关成纤维细胞重编程可促进肿瘤进展。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-10-30 DOI: 10.1111/gtc.13177
Tomoya Yamashita, Haruki Horiguchi, Tsuyoshi Kadomatsu, Michio Sato, Toshiro Moroishi, Yuichi Oike
{"title":"Immunotherapy-induced reprogramming of cancer-associated fibroblasts can promote tumor progression","authors":"Tomoya Yamashita,&nbsp;Haruki Horiguchi,&nbsp;Tsuyoshi Kadomatsu,&nbsp;Michio Sato,&nbsp;Toshiro Moroishi,&nbsp;Yuichi Oike","doi":"10.1111/gtc.13177","DOIUrl":"10.1111/gtc.13177","url":null,"abstract":"<p>Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy has advanced rapidly in the clinic; however, ICI initiation can also cause an unexpectedly rapid acceleration of cancer progression in some patients. Here, we used a murine syngeneic melanoma model to conduct mechanistic analysis of cancer-associated fibroblast (CAF) function in cancer progression in the context of immunotherapy. We found that after ICI treatment CAFs acquire inflammatory properties, which can promote tumor progression. Mechanistically, we show that T-cell-derived interferon-γ (IFN-γ) stimulates production of tumor necrosis factor-α (TNF-α) by macrophages, facilitating CAF conversion to inflammatory CAFs. Our findings suggest that CAF/immune cell crosstalk plays an essential role in ICI-associated tumor progression.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1275-1283"},"PeriodicalIF":1.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545061","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
Mrc1Claspin is essential for heterochromatin maintenance in Schizosaccharomyces pombe Mrc1Claspin对小鼠异染色质的维持至关重要。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-10-29 DOI: 10.1111/gtc.13175
Kei Kawakami, Yukari Ueno, Nao Hayama, Katsunori Tanaka
{"title":"Mrc1Claspin is essential for heterochromatin maintenance in Schizosaccharomyces pombe","authors":"Kei Kawakami,&nbsp;Yukari Ueno,&nbsp;Nao Hayama,&nbsp;Katsunori Tanaka","doi":"10.1111/gtc.13175","DOIUrl":"10.1111/gtc.13175","url":null,"abstract":"<p>In eukaryotes, maintenance of heterochromatin structure that represses gene expression during cell proliferation is essential for guaranteeing cell identity. However, how heterochromatin is maintained and transmitted to the daughter cells remains elusive. In this study, we constructed a reporter system to study the maintenance of heterochromatin in the subtelomeric region of the fission yeast, <i>Schizosaccharomyces pombe</i>. We demonstrated that once subtelomeric heterochromatin was established, it tended to be maintained as a metastable structure through cell proliferation. Using this system, we screened an <i>S. pombe</i> genome-wide gene deletion library for subtelomeric heterochromatin maintenance factors and identified 57 genes related to various cellular processes, in addition to well-characterized heterochromatin factors. We focused on Mrc1<sup>Claspin</sup>, a mediator of DNA replication checkpoint. We found that Mrc1 maintains heterochromatin structure not only at the subtelomeres but also at the pericentromeres and mating-type regions. Furthermore, we showed that Mrc1 is required for the localization of Snf2/Hdac-containing Repressor Complex (SHREC) and the maintenance of hypoacetylation state of histone H3K14. This study complements the recent discoveries that Mrc1 functions as a histone H3-H4 chaperone in heterochromatin maintenance.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1207-1224"},"PeriodicalIF":1.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545062","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
Pathogen challenge in Arabidopsis cotyledons induces enhanced disease resistance at newly formed rosette leaves via sustained upregulation of WRKY70 拟南芥子叶中的病原体挑战通过 WRKY70 的持续上调诱导新形成的莲座叶增强抗病性。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-10-28 DOI: 10.1111/gtc.13179
Kanoknipa Sukaoun, Tokuji Tsuchiya, Hiroshi Uchiyama
{"title":"Pathogen challenge in Arabidopsis cotyledons induces enhanced disease resistance at newly formed rosette leaves via sustained upregulation of WRKY70","authors":"Kanoknipa Sukaoun,&nbsp;Tokuji Tsuchiya,&nbsp;Hiroshi Uchiyama","doi":"10.1111/gtc.13179","DOIUrl":"10.1111/gtc.13179","url":null,"abstract":"<p>Pathogenic microorganisms often target seedlings shortly after germination. If plants exhibit resistance or resilience to pathogens, those exposed to pathogen challenge may grow further and form new unchallenged leaves. The purpose of this study was to examine disease resistance in the newly formed leaves of plants subjected to pathogen challenge. We used <i>Arabidopsis thaliana</i> and the oomycete pathogen <i>Hyaloperonospora arabidopsidis</i> (<i>Hpa</i>) as the model pathosystem. We found that Arabidopsis seedlings primarily challenged with the avirulent isolate <i>Hpa</i> exhibited enhanced disease resistance against the virulent isolate <i>Hpa</i> in newly formed rosette leaves (NFRLs). Our observations indicated that the transcript levels of the transcription factor gene <i>WRKY70</i>, which is essential for full resistance to the virulent isolate <i>Hpa</i>Noco2, were elevated and maintained at high levels in the NFRLs. In contrast, the transcript levels of the salicylic acid marker gene <i>PR1</i> and systemic acquired resistance-related genes did not exhibit sustained elevation. The maintenance of increased transcript levels of <i>WRKY70</i> operated independently of non-expressor of pathogenesis-related gene 1. These findings suggest that prolonged upregulation of <i>WRKY70</i> represents a defensive state synchronized with plant development to ensure survival against subsequent infections.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1236-1250"},"PeriodicalIF":1.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521735","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
Notch signaling pathway suppresses mRNA expression of hexokinase 2 under nutrient-poor conditions in U87-MG glioma cells Notch信号通路抑制了U87-MG胶质瘤细胞在营养匮乏条件下的己糖激酶2 mRNA表达。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-10-26 DOI: 10.1111/gtc.13176
Shuhei Kuwabara, Takamasa Mizoguchi, Jiawei Ma, Tohgo Kanoh, Yuki Ohta, Motoyuki Itoh
{"title":"Notch signaling pathway suppresses mRNA expression of hexokinase 2 under nutrient-poor conditions in U87-MG glioma cells","authors":"Shuhei Kuwabara,&nbsp;Takamasa Mizoguchi,&nbsp;Jiawei Ma,&nbsp;Tohgo Kanoh,&nbsp;Yuki Ohta,&nbsp;Motoyuki Itoh","doi":"10.1111/gtc.13176","DOIUrl":"10.1111/gtc.13176","url":null,"abstract":"<p>Control of nutrient homeostasis plays a central role in cell proliferation/survival during embryonic development and tumor growth. Activation of the Notch signaling pathway, a major contributor to cell–cell interactions, is a potential mechanism for cell adaptation to nutrient-poor conditions. Our previous study also demonstrated that during embryogenesis when nutrients such as glutamine and growth factors are potentially maintained at lower levels, Notch signaling suppresses mRNA expression of <i>hexokinase 2</i> (<i>hk2</i>), which is a glycolysis-associated gene, in the central nervous system. However, whether and how the genetic regulation of <i>HK2</i> via Notch signaling contributes to cellular adaptability to nutrient-poor environments remains unknown. In this study, we performed gene expression analysis using a U87-MG human glioma cell line and revealed that under conditions where both glutamine and serum were absent, Notch signaling was activated and <i>HK2</i> expression was downregulated by Notch signaling. We also found that Notch-mediated <i>HK2</i> suppression was triggered in a Notch ligand-selective manner. Furthermore, <i>HK2</i> was shown to inhibit cell proliferation of U87-MG gliomas, which might depend on Notch signaling activity. Together, our findings suggest the involvement of Notch-mediated <i>HK2</i> suppression in an adaptive mechanism of U87-MG glioma cells to nutrient-poor conditions.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1225-1235"},"PeriodicalIF":1.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499089","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
Roles of Pbp1, Mkt1, and Dhh1 in the regulation of gene expression in the medium containing non-fermentative carbon sources Pbp1、Mkt1 和 Dhh1 在含有非发酵性碳源的培养基中调控基因表达的作用。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-10-26 DOI: 10.1111/gtc.13174
Yurika Himeno, Nozomi Endo, Varsha Rana, Natsu Akitake, Tomomi Suda, Yasuyuki Suda, Tomoaki Mizuno, Kenji Irie
{"title":"Roles of Pbp1, Mkt1, and Dhh1 in the regulation of gene expression in the medium containing non-fermentative carbon sources","authors":"Yurika Himeno,&nbsp;Nozomi Endo,&nbsp;Varsha Rana,&nbsp;Natsu Akitake,&nbsp;Tomomi Suda,&nbsp;Yasuyuki Suda,&nbsp;Tomoaki Mizuno,&nbsp;Kenji Irie","doi":"10.1111/gtc.13174","DOIUrl":"10.1111/gtc.13174","url":null,"abstract":"<p>Pbp1, a yeast ortholog of human ataxin-2, is important for cell growth in the medium containing non-fermentable carbon sources. We had reported that Pbp1 regulates expression of genes related to glycogenesis via transcriptional regulation and genes related to mitochondrial function through mRNA stability control. To further analyze the role of Pbp1 in gene expression, we first examined the time course of gene expression after transfer from YPD medium containing glucose to YPGlyLac medium containing glycerol and lactate. At 12 h after transfer to YPGlyLac medium, the <i>pbp1∆</i> mutant showed decreased expression of genes related to mitochondrial function but no decrease in expression of glycogenesis-related genes. We also examined a role of the Pbp1-binding factor, Mkt1. The <i>mkt1∆</i> mutant, like the <i>pbp1∆</i> mutant, showed slow growth on YPGlyLac plate and reduced expression of genes related to mitochondrial function. Furthermore, we found that mutation of <i>DHH1</i> gene encoding a decapping activator exacerbated the growth of the <i>pbp1∆</i> mutant on YPGlyLac plate. The <i>dhh1∆</i> mutant showed reduced expression of genes related to mitochondrial function. These results indicate that Pbp1 and Mkt1 regulate the expression of genes related to mitochondrial function and that the decapping activator Dhh1 also regulates the expression of those genes.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1190-1206"},"PeriodicalIF":1.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499090","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
Investigation of exon skipping therapy in kidney organoids from Alport syndrome patients derived iPSCs 研究从 Alport 综合征患者衍生的 iPSCs 肾脏器官组织中跳过外显子的疗法。
IF 1.3 4区 生物学
Genes to Cells Pub Date : 2024-10-22 DOI: 10.1111/gtc.13170
Kensuke Yabuuchi, Tomoko Horinouchi, Tomohiko Yamamura, Kandai Nozu, Minoru Takasato
{"title":"Investigation of exon skipping therapy in kidney organoids from Alport syndrome patients derived iPSCs","authors":"Kensuke Yabuuchi,&nbsp;Tomoko Horinouchi,&nbsp;Tomohiko Yamamura,&nbsp;Kandai Nozu,&nbsp;Minoru Takasato","doi":"10.1111/gtc.13170","DOIUrl":"10.1111/gtc.13170","url":null,"abstract":"<p>Alport syndrome (AS) is a hereditary disease caused by mutations in the <i>COL4A5</i> gene and leads to chronic kidney disease. Currently, no specific treatment has been developed. However, a recent study using AS-model mice demonstrated that the exon skipping method could partially rescue the symptoms. In this study, we evaluated the effects of the exon skipping method using kidney organoids generated from AS-patient-derived induced pluripotent stem cells (AS-iPSCs). We generated kidney organoids from AS-iPSCs, which exhibited nephron structures. As expected, the C-terminus of COL4A5 was not expressed in AS-organoids. Interestingly, anti-sense oligonucleotides restored the expression of the C-terminus of COL4A5 in vitro. Next, we transplanted AS-organoids into mice and evaluated glomerular basement membrane formation in vivo. We found that AS-organoids formed a lower slit diaphragm ratio compared to control organoids. Finally, we assessed the effects of exon skipping on transplanted organoids but observed minimum effects. These studies suggest that AS-iPSCs can generate kidney organoids lacking the C-terminus of COL4A5, and that exon skipping can induce its expression in vitro.</p>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1118-1130"},"PeriodicalIF":1.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463122","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
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