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Long noncoding RNA xIST:Mechanisms for x chromosome inactivation,roles in sex-biased diseases,and therapeutic opportunities

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Genes & Diseases 2022年第6期9卷 1478-1492页

作者： Jianjian Li Zhe Ming Liuyi Yang Tingxuan Wang Gaowen Liu Qing Ma Shenzhen Key Laboratory of Synthetic Genomics Guangdong Provincial Key Laboratory of Synthetic GenomicsCAS Key Laboratory of Quantitative Engineering BiologyShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055PR China

Sexual dimorphism has been reported in various human diseases including autoimmune diseases,neurological diseases,pulmonary arterial hypertension,and some types of cancers,although the underlying mechanisms remain poorly *** long noncoding RNA(lncRNA)x-inactive specific transcript(xIST)is involved in x chromosome inactivation(xCI)in female placental mammals,a process that ensures the balanced expression dosage of x-linked genes between *** is abnormally expressed in many sex-biased *** addition,escape from xIST-mediated xCI and skewed xCI also contribute to sex-biased ***,its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased *** manipulation of xIST expression can inhibit the progression of some of these diseases in animal models,and therefore xIST has been proposed as a potential therapeutic *** this manuscript,we summarize the current knowledge about the mechanisms for xIST-mediated xCI and the roles of xIST in sex-biased diseases,and discuss potential therapeutic strategies targeting xIST.

关键词： Epigenetic regulation Long noncoding RNA Sex-biased diseases x chromosome inactivation xIST

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Low xIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra x chromosome

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Asian Journal of Andrology 2023年第6期25卷 662-673页

作者： Liang-Yu Zhao Peng Li Chen-Cheng Yao Ru-Hui Tian Yu-xin Tang Yu-Zhuo Chen Zhi Zhou Zheng Li Department of Andrology The Center for Men’s HealthUrologic Medical CenterShanghai Key Laboratory of Reproductive MedicineShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Urology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China Department of Interventional Medicine Guangdong Provincial Key Laboratory of Biomedical ImagingThe Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China School of Life Science and Technology ShanghaiTech UniversityShanghai 200120China

Klinefelter syndrome(KS)is the most common genetic cause of human male ***,the effect of the extra x chromosome on different testicular cell types remains poorly ***,we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control *** the different somatic cells,Sertoli cells showed the greatest transcriptome changes in KS *** analysis showed that x-inactive-specific transcript(xIST),a key factor that inactivates one x chromosome in female mammals,was widely expressed in each testicular somatic cell type but not in Sertoli *** loss of xIST in Sertoli cells leads to an increased level of x chromosome genes,and further disrupts their transcription pattern and cellular *** phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial *** results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial *** study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific x chromosome inactivation failure.

关键词： Klinefelter syndrome nonobstructive azoospermia Sertoli cell spermatogenesis x chromosome inactivation

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Search for naive human pluripotent stem cells

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World Journal of Stem Cells 2015年第3期7卷 649-656页

作者： Simone Aparecida Siqueira Fonseca Roberta Montero Costas Lygia Veiga Pereira National Laboratory of Embryonic Stem Cell Department of Genetics and Evolutionary Biology University of Sao Paulo Sao Paulo 05508-090 Brazil

Normal mouse pluripotent stem cells were originally derived from the inner cell mass(ICM) of blastocysts and shown to be the in vitro equivalent of those pre-implantation embryonic cells, and thus were called embryonic stem cells(ESCs). More than a decade later, pluripotent cells were isolated from the ICM of human blastocysts. Despite being called human ESCs, these cells differ significantly from mouse ESCs, including different morphology and mechanisms of control of pluripotency, suggesting distinct embryonic origins of ESCs from the two species. Subsequently, mouse pluripotent stem cells were established from the ICMderived epiblast of post-implantation embryos. These mouse epiblast stem cells(Epi SCs) are morphological and epigenetically more similar to human ESCs. This raised the question of whether cells from the human ICM are in a more advanced differentiation stage than their murine counterpart, or whether the available culture conditions were not adequate to maintain those human cells in their in vivo state, leading to a transition into Epi SC-like cells in vitro. More recently, novel culture conditions allowed the conversion of human ESCs into mouse ESC-like cells called nave(or ground state) human ESCs, and the derivation of nave human ESCs from blastocysts. Here we will review the characteristics of each type of pluripotent stem cells, how(and whether) these relate to different stages of embryonic development, and discuss the potential implications of nave human ESCs in research and therapy.

关键词： Naive pluripotent stem cells Epiblast stem cells x chromosome inactivation Human embryonic stem cells

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