{"title":"胚泡互补产生的种间嵌合体中大鼠肺上皮细胞的成熟状态","authors":"Yamato Murata, Shunsuke Yuri, Masahito Ikawa, Ayako Isotani","doi":"10.1111/gtc.70046","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>This study investigates the maturation status of rat lung epithelial cells in interspecies chimeras generated via blastocyst complementation (BC) using <i>Fgfr2b</i>-knockout mouse embryos. In our previous study, we succeeded in generating rat-derived lung epithelium in interspecies chimeras using tetraploid complementation; however, the resulting cells remained immature and failed to support respiratory function. In this study, we established two <i>Fgfr2b</i>-KO mouse lines via CRISPR/Cas9 and injected GFP-labeled rat embryonic stem (ES) cells into blastocysts, which were then transferred to pseudopregnant female mice. Comparative histological analysis of airway spaces between wild-type rat lungs (E19.5–E21.5) and BC chimeras revealed that BC lungs reached a maturation stage comparable to E20.5–E21.5 rat lungs. Quantitative Polymerase Chain Reaction of key epithelial maturation markers—including ENaC subunits, Aqp5, and surfactant protein genes—demonstrated late-gestational upregulation in wild-type rat lungs, while expression levels in BC lungs exhibited significant inter-individual variability, corresponding to stages between E19.5 and E21.5 in wild-type rats. These findings suggest that the mouse host environment may partially promote maturation of rat-derived lung epithelial cells; however, additional mechanisms are likely required to achieve functional respiratory capacity.</p>\n </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 5","pages":""},"PeriodicalIF":1.3000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Maturation Status of Rat Lung Epithelial Cells in Interspecies Chimeras Generated by Blastocyst Complementation\",\"authors\":\"Yamato Murata, Shunsuke Yuri, Masahito Ikawa, Ayako Isotani\",\"doi\":\"10.1111/gtc.70046\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>This study investigates the maturation status of rat lung epithelial cells in interspecies chimeras generated via blastocyst complementation (BC) using <i>Fgfr2b</i>-knockout mouse embryos. In our previous study, we succeeded in generating rat-derived lung epithelium in interspecies chimeras using tetraploid complementation; however, the resulting cells remained immature and failed to support respiratory function. In this study, we established two <i>Fgfr2b</i>-KO mouse lines via CRISPR/Cas9 and injected GFP-labeled rat embryonic stem (ES) cells into blastocysts, which were then transferred to pseudopregnant female mice. Comparative histological analysis of airway spaces between wild-type rat lungs (E19.5–E21.5) and BC chimeras revealed that BC lungs reached a maturation stage comparable to E20.5–E21.5 rat lungs. Quantitative Polymerase Chain Reaction of key epithelial maturation markers—including ENaC subunits, Aqp5, and surfactant protein genes—demonstrated late-gestational upregulation in wild-type rat lungs, while expression levels in BC lungs exhibited significant inter-individual variability, corresponding to stages between E19.5 and E21.5 in wild-type rats. These findings suggest that the mouse host environment may partially promote maturation of rat-derived lung epithelial cells; however, additional mechanisms are likely required to achieve functional respiratory capacity.</p>\\n </div>\",\"PeriodicalId\":12742,\"journal\":{\"name\":\"Genes to Cells\",\"volume\":\"30 5\",\"pages\":\"\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes to Cells\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/gtc.70046\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes to Cells","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gtc.70046","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Maturation Status of Rat Lung Epithelial Cells in Interspecies Chimeras Generated by Blastocyst Complementation
This study investigates the maturation status of rat lung epithelial cells in interspecies chimeras generated via blastocyst complementation (BC) using Fgfr2b-knockout mouse embryos. In our previous study, we succeeded in generating rat-derived lung epithelium in interspecies chimeras using tetraploid complementation; however, the resulting cells remained immature and failed to support respiratory function. In this study, we established two Fgfr2b-KO mouse lines via CRISPR/Cas9 and injected GFP-labeled rat embryonic stem (ES) cells into blastocysts, which were then transferred to pseudopregnant female mice. Comparative histological analysis of airway spaces between wild-type rat lungs (E19.5–E21.5) and BC chimeras revealed that BC lungs reached a maturation stage comparable to E20.5–E21.5 rat lungs. Quantitative Polymerase Chain Reaction of key epithelial maturation markers—including ENaC subunits, Aqp5, and surfactant protein genes—demonstrated late-gestational upregulation in wild-type rat lungs, while expression levels in BC lungs exhibited significant inter-individual variability, corresponding to stages between E19.5 and E21.5 in wild-type rats. These findings suggest that the mouse host environment may partially promote maturation of rat-derived lung epithelial cells; however, additional mechanisms are likely required to achieve functional respiratory capacity.
期刊介绍:
Genes to Cells provides an international forum for the publication of papers describing important aspects of molecular and cellular biology. The journal aims to present papers that provide conceptual advance in the relevant field. Particular emphasis will be placed on work aimed at understanding the basic mechanisms underlying biological events.