Science China Life Sciences最新文献

{"title":"Versatile and efficient mammalian genome editing with Type I-C CRISPR System of Desulfovibrio vulgaris.","authors":"Pan Li, Dingcai Dong, Fei Gao, Yuyang Xie, Honglin Huang, Siwei Sun, Zhao Ma, Cheng He, Jinsheng Lai, Xuguang Du, Sen Wu","doi":"10.1007/s11427-023-2682-5","DOIUrl":"10.1007/s11427-023-2682-5","url":null,"abstract":"<p><p>CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins. While type I CRISPR systems in Class I may offer greater specificity and versatility, they are not well-developed for genome editing. Here, we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris (Dvu) for efficient and precise genome editing in mammalian cells and animals. We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy. These edited pig cells can serve as donors for generating transgenic cloned piglets. The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair. Additionally, we adapted the Dvu-Cascade effector for cytosine and adenine base editing, developing Dvu-CBE and Dvu-ABE systems. These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks. Off-target analysis confirmed the high specificity of the Dvu type I-C editor. Our findings demonstrate the Dvu type I-C editor's potential for diverse mammalian genome editing applications, including deletions, fragment replacement, and base editing, with high efficiency and specificity for biomedicine and agriculture.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2471-2487"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the PGC-1α-mediated mitochondrial glutamine metabolism pathway attenuates female offspring osteoarthritis induced by prenatal excessive prednisone.","authors":"Qingxian Li, Fan Zhang, Yongguo Dai, Liang Liu, Liaobin Chen, Hui Wang","doi":"10.1007/s11427-023-2593-4","DOIUrl":"10.1007/s11427-023-2593-4","url":null,"abstract":"<p><p>Osteoarthritis is a chronic, age-related joint disease. Previous studies have shown that osteoarthritis develops during intrauterine development. Prednisone is frequently used to treat pregnancies complicated by autoimmune diseases. However, limited research has been conducted on the enduring effects of prednisone use during pregnancy on the offspring. In this study, we investigated the effect of excessive prednisone exposure on cartilage development and susceptibility to osteoarthritis in the offspring. We found that prenatal prednisone exposure (PPE) impaired cartilage extracellular matrix (ECM) synthesis, resulting in poor cartilage pathology in female offspring during the adult period, which was further exacerbated after long-distance running stimulation. Additionally, PPE suppressed cartilage development during the intrauterine period. Tracing back to the intrauterine period, we found that Pred, rather than prednisone, decreased glutamine metabolic flux, which resulted in increased oxidative stress, and decreased histone acetylation, and expression of cartilage phenotypic genes. Further, PGC-1α-mediated mitochondrial biogenesis, while PPE caused hypermethylation in the promoter region of PGC-1α and decreased its expression in fetal cartilage by activating the glucocorticoid receptor, resulting in a reduction of glutamine flux controlled by mitochondrial biogenesis. Additionally, overexpression of PGC-1α (either pharmacological or through lentiviral transfection) reversed PPE- and Pred-induced cartilage ECM synthesis impairment. In summary, this study demonstrated that PPE causes chondrodysplasia in female offspring and increases their susceptibility to postnatal osteoarthritis. Hence, targeting PGC-1α early on could be a potential intervention strategy for PPE-induced osteoarthritis susceptibility.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2382-2397"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zika virus infection induces glycometabolic disorder in northern pig-tailed macaques.","authors":"Qing Li, Ren-Hua Yang, Yan Hu, Bei-Bei Tang, Ying-Jie Jiang, Chang-Bo Zheng, Tian-Zhang Song","doi":"10.1007/s11427-024-2663-6","DOIUrl":"10.1007/s11427-024-2663-6","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2527-2529"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgens exert multifaceted functions in sex differences analyzed through single-cell transcriptome.","authors":"Xinxin Tang, Yinkun Fu, Zhihui Zou, Yue Li, Ming He","doi":"10.1007/s11427-024-2652-y","DOIUrl":"10.1007/s11427-024-2652-y","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2530-2531"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature regulates negative supercoils to modulate meiotic crossovers and chromosome organization.","authors":"Yingjin Tan, Taicong Tan, Shuxian Zhang, Bo Li, Beiyi Chen, Xu Zhou, Ying Wang, Xiao Yang, Binyuan Zhai, Qilai Huang, Liangran Zhang, Shunxin Wang","doi":"10.1007/s11427-024-2671-1","DOIUrl":"10.1007/s11427-024-2671-1","url":null,"abstract":"<p><p>Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes (homologs) together for their faithful segregation, while promoting genetic diversity of the progeny. The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes. Environmental factors, especially temperature, also play an important role in modulating crossovers. However, it is unclear how temperature affects crossovers. Here, we examined the distribution of budding yeast axis components (Red1, Hop1, and Rec8) and the crossover-associated Zip3 foci in detail at different temperatures, and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers. Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci. Most importantly, temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils. These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization. These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic recombination and chromosome organization, with important implications for evolution and breeding.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2426-2443"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-genome sequencing identifies novel genes for autism in Chinese trios.","authors":"Suhua Chang, Jia Jia Liu, Yilu Zhao, Tao Pang, Xiangyu Zheng, Zhirui Song, Anyi Zhang, Xuping Gao, Lingxue Luo, Yanqing Guo, Jing Liu, Li Yang, Lin Lu","doi":"10.1007/s11427-023-2564-8","DOIUrl":"10.1007/s11427-023-2564-8","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high genetic heritability but heterogeneity. Fully understanding its genetics requires whole-genome sequencing (WGS), but the ASD studies utilizing WGS data in Chinese population are limited. In this study, we present a WGS study for 334 individuals, including 112 ASD patients and their non-ASD parents. We identified 146 de novo variants in coding regions in 85 cases and 60 inherited variants in coding regions. By integrating these variants with an association model, we identified 33 potential risk genes (P<0.001) enriched in neuron and regulation related biological process. Besides the well-known ASD genes (SCN2A, NF1, SHANK3, CHD8 etc.), several high confidence genes were highlighted by a series of functional analyses, including CTNND1, DGKZ, LRP1, DDN, ZNF483, NR4A2, SMAD6, INTS1, and MRPL12, with more supported evidence from GO enrichment, expression and network analysis. We also integrated RNA-seq data to analyze the effect of the variants on the gene expression and found 12 genes in the individuals with the related variants had relatively biased expression. We further presented the clinical phenotypes of the proband carrying the risk genes in both our samples and Caucasian samples to show the effect of the risk genes on phenotype. Regarding variants in non-coding regions, a total of 74 de novo variants and 30 inherited variants were predicted as pathogenic with high confidence, which were mapped to specific genes or regulatory features. The number of de novo variants found in patient was significantly associated with the parents' ages at the birth of the child, and gender with trend. We also identified small de novo structural variants in ASD trios. The results in this study provided important evidence for understanding the genetic mechanism of ASD.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2368-2381"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling potential sex-determining genes and sex-specific markers in autotetraploid Carassius auratus.","authors":"Kun Zhang, Xu Huang, Chongqing Wang, Xidan Xu, Xiaowei Xu, Xiaoping Dong, Qingwen Xiao, Jinhai Bai, Yue Zhou, Zhengkun Liu, Xinyi Deng, Yan Tang, Siyang Li, Enkui Hu, Wanjing Peng, Ling Xiong, Qinbo Qin, Shaojun Liu","doi":"10.1007/s11427-023-2694-5","DOIUrl":"10.1007/s11427-023-2694-5","url":null,"abstract":"<p><p>Autotetraploid Carassius auratus is a stable hereditary autotetraploid fish resulting from the hybridization of Carassius auratus red var. (RCC, ♀) × Megalobrama amblycephala (BSB, ♂), containing four sets of RCC chromosomes. However, the molecular mechanism underlying the determination of sex in this species remains largely unknown. Currently, there lacks a full understanding of the molecular mechanisms governing sex determination and specific molecular markers to differentiate sex in this species. In this study, 25,801,677 SNPs (Single-nucleotide polymorphism) and 6,210,306 Indels (insertion-deletion) were obtained from whole-genome resequencing of 100 individuals (including 50 female and 50 male). Further identification confirmed the candidate chromosomes as Chr46B, with the sex-determining region located at Chr46B: 22,500,000-22,800,000 bp. Based on the male-specific insertion (26 bp) within the candidate sex-determining region, a pair of sex-specific molecular markers has been identified. In addition, based on the screening of candidate sex-determining region genes and RT-qPCR validation analysis, ADAM10, AQP9 and tc1a were identified as candidate sex-determining genes. These findings provide a robust foundation for investigating sex determination mechanisms in fish, the evolution of sex chromosomes, and the development of monosex populations.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2444-2458"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RpL38 modulates germ cell differentiation by controlling Bam expression in Drosophila testis.","authors":"Yang Fang, Fengchao Zhang, Fangzhen Zhao, Jiajia Wang, Xinkai Cheng, Fei Ye, Jiayu He, Long Zhao, Ying Su","doi":"10.1007/s11427-024-2646-3","DOIUrl":"10.1007/s11427-024-2646-3","url":null,"abstract":"<p><p>Switching from mitotic spermatogonia to meiotic spermatocytes is critical to producing haploid sperms during male germ cell differentiation. However, the underlying mechanisms of this switch remain largely unexplored. In Drosophila melanogaster, the gene RpL38 encodes the ribosomal protein L38, one component of the 60S subunit of ribosomes. We found that its depletion in spermatogonia severely diminished the production of mature sperms and thus led to the infertility of male flies. By examining the germ cell differentiation in testes, we found that RpL38-knockdown blocked the transition from spermatogonia to spermatocytes and accumulated spermatogonia in the testis. To understand the intrinsic reason for this blockage, we conducted proteomic analysis for these spermatogonia populations. Differing from the control spermatogonia, the accumulated spermatogonia in RpL38-knockdown testes already expressed many spermatocyte markers but lacked many meiosis-related proteins, suggesting that spermatogonia need to prepare some important proteins for meiosis to complete their switch into spermatocytes. Mechanistically, we found that the expression of bag of marbles (bam), a crucial determinant in the transition from spermatogonia to spermatocytes, was inhibited at both the mRNA and protein levels upon RpL38 depletion. We also confirmed that the bam loss phenocopied RpL38 RNAi in the testis phenotype and transcriptomic profiling. Strikingly, overexpressing bam was able to fully rescue the testis abnormality and infertility of RpL38-knockdown flies, indicating that bam is the key effector downstream of RpL38 to regulate spermatogonia differentiation. Overall, our data suggested that germ cells start to prepare meiosis-related proteins as early as the spermatogonial stage, and RpL38 in spermatogonia is required to regulate their transition toward spermatocytes in a bam-dependent manner, providing new knowledge for our understanding of the transition process from spermatogonia to spermatocytes in Drosophila spermatogenesis.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2411-2425"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSC-mediated mitochondrial transfer restores mitochondrial DNA and function in neural progenitor cells of Leber's hereditary optic neuropathy.","authors":"Rui Wang, Feixiang Bao, Manjiao Lu, Xiaoyun Jia, Jiahui Xiao, Yi Wu, Qingjiong Zhang, Xingguo Liu","doi":"10.1007/s11427-024-2647-8","DOIUrl":"10.1007/s11427-024-2647-8","url":null,"abstract":"<p><p>Leber's hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA (mtDNA). Unfortunately, the available treatment options for LHON patients are limited due to challenges in mitochondrial replacement. In our study, we reprogramming LHON urine cells into induced pluripotent stem cells (iPSCs) and differentiating them into neural progenitor cells (NPCs) and neurons for disease modeling. Our research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function, confirming the disease phenotype. However, through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells (MSCs), we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON neurons. These findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs, even after their differentiation into neurons. This discovery holds promise as a potential therapeutic strategy for LHON patients.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2511-2519"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huangjing is not only a good medicine but also an affordable healthy diet.","authors":"Donghong Chen, Dun Si, Jingjing Liu, Jinping Si","doi":"10.1007/s11427-024-2713-1","DOIUrl":"10.1007/s11427-024-2713-1","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2520-2522"},"PeriodicalIF":8.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}