Genes to Cells最新文献_第9页

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, Tomoko Horinouchi, Tomohiko Yamamura, Kandai Nozu, Minoru Takasato","doi":"10.1111/gtc.13170","DOIUrl":"10.1111/gtc.13170","url":null,"abstract":"Alport syndrome (AS) is a hereditary disease caused by mutations in the COL4A5 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.","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

Loss of a single Zn finger, but not that of two Zn fingers, of GATA3 drives skin inflammation GATA3 单个锌指（而非两个锌指）的缺失会引发皮肤炎症。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-22 DOI: 10.1111/gtc.13171

Tomohiro Iguchi, Makiko Toma-Hirano, Masakatsu Takanashi, Hisao Masai, Shoichiro Miyatake

{"title":"Loss of a single Zn finger, but not that of two Zn fingers, of GATA3 drives skin inflammation","authors":"Tomohiro Iguchi, Makiko Toma-Hirano, Masakatsu Takanashi, Hisao Masai, Shoichiro Miyatake","doi":"10.1111/gtc.13171","DOIUrl":"10.1111/gtc.13171","url":null,"abstract":"Transcription factor GATA3 is essential for the developmental processes of T cells. Recently, the silencer of a cytokine IFNγ gene was identified, the inhibitory activity of which requires GATA3. GATA3 has 2 Zn fingers and the commonly used GATA3 deficient mice lack both fingers (D2). We have established a mouse line that lacks only one Zn finger close to the C terminus (D1). The D1 mice line developed dermatitis, which was not observed in D2 mice. The expression of S100a8/S100a9 was elevated in D1 to a level higher than in D2, suggesting their roles in dermatitis development. CD8 T cells of both D1 and D2 lines expressed inhibitory receptors associated with the exhausted state. In the absence of MHC class II, the skin inflammation was exacerbated in both lines. The gene expression pattern of CD8 T cells became similar to that of effector T cells. Blocking Ab against LAG3 upregulated the expression of the effector molecules of T cells. These results suggest that the disfunction of GATA3 can lead to the spontaneous activation of CD8 T cells that causes skin inflammation, and that suppressive activity of MHC class II - LAG3 interaction ameliorates dermatitis development.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1173-1189"},"PeriodicalIF":1.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463123","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 and characterization of an enhancer element regulating expression of Cdkn1c (p57 gene) 调控 Cdkn1c（p57 基因）表达的增强子元件的鉴定和表征。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-11 DOI: 10.1111/gtc.13173

Daisuke Koga, Shogo Nakayama, Tsunaki Higa, Keiichi I. Nakayama

引用次数: 0

Cellular and molecular mechanisms of asymmetric stem cell division in tissue homeostasis 组织稳态中不对称干细胞分裂的细胞和分子机制

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-08 DOI: 10.1111/gtc.13172

Sema Bolkent

引用次数: 0

The scaffold protein IQGAP1 promotes reorientation of epithelial cell polarity at the two-cell stage for cystogenesis 支架蛋白 IQGAP1 可促进上皮细胞极性在双细胞阶段的重新定向，从而促进囊肿生成。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-08 DOI: 10.1111/gtc.13169

Michihiro Horikawa, Junya Hayase, Sachiko Kamakura, Akira Kohda, Masafumi Nakamura, Hideki Sumimoto

{"title":"The scaffold protein IQGAP1 promotes reorientation of epithelial cell polarity at the two-cell stage for cystogenesis","authors":"Michihiro Horikawa, Junya Hayase, Sachiko Kamakura, Akira Kohda, Masafumi Nakamura, Hideki Sumimoto","doi":"10.1111/gtc.13169","DOIUrl":"10.1111/gtc.13169","url":null,"abstract":"A single epithelial cell embedded in extracellular matrix (ECM) can proliferate to form an apical lumen-harboring cyst, whose formation is a fundamental step in epithelial organ development. At an early two-cell stage after cell division, the cell doublet typically displays “inverted” polarity, with apical and basolateral proteins being located to the ECM-facing and cell–cell-contacting plasma membranes, respectively. Correct cystogenesis requires polarity reorientation, a process containing apical protein endocytosis from the ECM-abutting periphery and subsequent apical vesicle delivery to a cell–cell contact site for lumen formation. Here, we show that downstream of the ECM-signal-transducer β1-integrin, Rac1, and its effector IQGAP1 promote apical protein endocytosis, contributing to polarity reorientation of mammalian epithelial Madin-Darby canine kidney (MDCK) cells at a later two-cell stage in three-dimensional culture. Rac1–GTP facilitates IQGAP1 interaction with the Rac-specific activator Tiam1, which also contributes to the endocytosis and enhances the effect of IQGAP1. These findings suggest that Tiam1 and IQGAP1 form a positive feedback loop to activate Rac1. With Rac1–GTP, IQGAP1 also binds to AP2α, an adaptor protein subunit for clathrin-mediated endocytosis; depletion of the AP2 complex impairs apical protein endocytosis in MDCK doublets. Thus, Rac1 likely participates in polarity reorientation at the two-cell stage via its interaction with IQGAP1.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1154-1172"},"PeriodicalIF":1.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389828","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

Evolution of the Cdk4/6–Cdkn2 system in invertebrates 无脊椎动物中 Cdk4/6-Cdkn2 系统的进化。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-08 DOI: 10.1111/gtc.13165

Shiori Yuki, Shunsuke Sasaki, Yuta Yamamoto, Fumika Murakami, Kazumi Sakata, Isato Araki

引用次数: 0

Roles of ZEB1 and ZEB2 in E-cadherin expression and cell aggressiveness in head and neck cancer ZEB1和ZEB2在头颈癌E-粘连蛋白表达和细胞侵袭性中的作用

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-03 DOI: 10.1111/gtc.13167

Arisa Kinouchi, Takahiro Jubashi, Rikito Tatsuno, Jiro Ichikawa, Kaname Sakamoto, Daiju Sakurai, Tomonori Kawasaki, Hiroki Ishii, Keiji Miyazawa, Masao Saitoh

{"title":"Roles of ZEB1 and ZEB2 in E-cadherin expression and cell aggressiveness in head and neck cancer","authors":"Arisa Kinouchi, Takahiro Jubashi, Rikito Tatsuno, Jiro Ichikawa, Kaname Sakamoto, Daiju Sakurai, Tomonori Kawasaki, Hiroki Ishii, Keiji Miyazawa, Masao Saitoh","doi":"10.1111/gtc.13167","DOIUrl":"10.1111/gtc.13167","url":null,"abstract":"Zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in cancer cell differentiation and metastasis, and has been well studied in the field of cancer cell biology. ZEB2 has a highly similar conformation to ZEB1, but its role in head and neck squamous cell carcinoma (HNSCC) cells is not fully understood. Here, we separately overexpressed ZEB1 and ZEB2 in C57BL/6 mouse oral cancer (MOC) cells and investigated their cellular characteristics, including E-cadherin levels, motile properties, chemoresistance, and metastatic ability in immunocompetent mice. Both ZEB1 and ZEB2 overexpression reduced epithelial traits and converted cells to an aggressive phenotype. Surprisingly, ZEB1 overexpression increased the endogenous level of ZEB2 in MOC cells, and vice versa. The molecular mechanisms underlying these findings remain unclear. However, the in vitro anchorage-independent growth of MOC cells overexpressing ZEB2 was considerably greater than that of MOC cells overexpressing ZEB1. These findings suggest that ZEB2, like ZEB1, has the ability to induce the differentiation of cancer cells into those with highly aggressive traits.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1131-1143"},"PeriodicalIF":1.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371639","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

Regular exercise suppresses steatosis-associated liver cancer development by degrading E2F1 and c-Myc via circadian gene upregulation 通过昼夜节律基因上调降解E2F1和c-Myc，定期运动可抑制脂肪变性相关肝癌的发展。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-10-02 DOI: 10.1111/gtc.13161

Vu Thuong Huyen, Kanae Echizen, Ryota Yamagishi, Miho Kumagai, Yoshiki Nonaka, Takahiro Kodama, Tatsuya Ando, Megumu Yano, Naoki Takada, Masaki Takasugi, Fumitaka Kamachi, Naoko Ohtani

{"title":"Regular exercise suppresses steatosis-associated liver cancer development by degrading E2F1 and c-Myc via circadian gene upregulation","authors":"Vu Thuong Huyen, Kanae Echizen, Ryota Yamagishi, Miho Kumagai, Yoshiki Nonaka, Takahiro Kodama, Tatsuya Ando, Megumu Yano, Naoki Takada, Masaki Takasugi, Fumitaka Kamachi, Naoko Ohtani","doi":"10.1111/gtc.13161","DOIUrl":"10.1111/gtc.13161","url":null,"abstract":"Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis-associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development. To explore the underlying mechanisms, we examined the gene expression profiles in the livers of the exercise and non-exercise groups. The expressions of circadian genes, such as Per1 and Cry2, were upregulated in the exercise group. As circadian rhythm disruption is known to cause various diseases, including cancer, improving circadian rhythm through exercise could contribute to cancer prevention. We further found that the expression of a series of E2F1 and c-Myc target genes that directly affect the proliferation of cancer cells was downregulated in the exercise group. However, the expression of E2F1 and c-Myc was transcriptionally unchanged but degraded at the post-translational level by exercise. Cry2, which is regulated by the Skp1-Cul1-FBXL3 (SCFFBXL3) ubiquitin ligase complex by binding to FBXL3, can form a complex with E2F1 and c-Myc, which we think is the mechanism to degrade them. Our study revealed a previously unknown mechanism by which exercise prevents cancer development.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"1012-1025"},"PeriodicalIF":1.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365047","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

Search for putative gene regulatory motifs in CAHS3, linked to anhydrobiosis in a tardigrade Ramazzottius varieornatus, in vivo and in silico 寻找 CAHS3 中的推定基因调控基团，在体内和硅学中研究与迟行龙 Ramazzottius varieornatus 的无水生物症有关的基因调控基团。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-30 DOI: 10.1111/gtc.13168

Sora Ishikawa, Sae Tanaka, Kazuharu Arakawa

{"title":"Search for putative gene regulatory motifs in CAHS3, linked to anhydrobiosis in a tardigrade Ramazzottius varieornatus, in vivo and in silico","authors":"Sora Ishikawa, Sae Tanaka, Kazuharu Arakawa","doi":"10.1111/gtc.13168","DOIUrl":"10.1111/gtc.13168","url":null,"abstract":"Tardigrades possess the ability to enter an almost completely dehydrated state, anhydrobiosis. The CAHS (cytosolic abundant heat-soluble) protein family has been identified as one of the anhydrobiosis-related proteins. In particular, CAHS3 protein from an anhydrobiotic tardigrade, Ramazzottius varieornatus, shows heat-solubility and reversible condensation and is one of the most highly expressed among the CAHS paralogs. A recently developed tardigrade-specific vector showed tissue-specific expression of RvCAHS3 most pronounced in the epidermis in vivo, contrary to the idea that anhydrobiotic genes are uniformly expressed in all tardigrade cells. In this study, we investigated the regulation of RvCAHS3 gene expression through in vivo expression experiments using tardigrade vectors with a series of truncated upstream regions coupled with in silico analysis to identify the anhydrobiosis-related genes that are expressed under the same regulatory system as RvCAHS3. As a result, the 300–350 bp region upstream of RvCAHS3 is critical for regulating gene expression in tardigrade vector experiments, and three motifs conserved between two species of anhydrobiotic tardigrades were identified within a 500 bp region directly upstream of RvCAHS3 start codon. These motifs, which have also been identified upstream of other CAHS genes, could be associated with the regulatory system of anhydrobiosis-related genes in tardigrades.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 12","pages":"1144-1153"},"PeriodicalIF":1.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gtc.13168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345083","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

Meta-analysis of gonadal transcriptome provides novel insights into sex change mechanism across protogynous fishes 性腺转录组的元分析为了解原雌性鱼类的性别变化机制提供了新的视角。

IF 1.3 4区生物学

Genes to Cells Pub Date : 2024-09-29 DOI: 10.1111/gtc.13166

Ryo Nozu, Mitsutaka Kadota, Masaru Nakamura, Shigehiro Kuraku, Hidemasa Bono

{"title":"Meta-analysis of gonadal transcriptome provides novel insights into sex change mechanism across protogynous fishes","authors":"Ryo Nozu, Mitsutaka Kadota, Masaru Nakamura, Shigehiro Kuraku, Hidemasa Bono","doi":"10.1111/gtc.13166","DOIUrl":"10.1111/gtc.13166","url":null,"abstract":"Protogyny, being capable of changing from female to male during their lifetime, is prevalent in 20 families of teleosts but is believed to have evolved within specific evolutionary lineages. Therefore, shared regulatory factors governing the sex change process are expected to be conserved across protogynous fishes. However, a comprehensive understanding of this mechanism remains elusive. To identify these factors, we conducted a meta-analysis using gonadal transcriptome data from seven species. We curated data pairs of ovarian tissue and transitional gonad, and employed ratios of expression level as a unified criterion for differential expression, enabling a meta-analysis across species. Our approach revealed that classical sex change-related genes exhibited differential expression levels between the ovary and transitional gonads, consistent with previous reports. These results validate our methodology's robustness. Additionally, we identified novel genes not previously linked to gonadal sex change in fish. Notably, changes in the expression levels of acetoacetyl-CoA synthetase and apolipoprotein Eb, which are involved in cholesterol synthesis and transport, respectively, suggest that the levels of cholesterol, a precursor of steroid hormones crucial for sex change, are decreased upon sex change onset in the gonads. This implies a potential universal influence of cholesterol dynamics on gonadal transformation in protogyny.","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"29 11","pages":"1052-1068"},"PeriodicalIF":1.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345082","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