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The chemical reprogramming of unipotent adult germ cells towards authentic pluripotency and de novo establishment of imprinting

作     者:Yuhan Chen Jiansen Lu Yanwen Xu Yaping Huang Dazhuang Wang Peiling Liang Shaofang Ren Xuesong Hu Yewen Qin Wei Ke Ralf Jauch Andrew Paul Hutchins Mei Wang Fuchou Tang Xiao-Yang Zhao Yuhan Chen;Jiansen Lu;Yanwen Xu;Yaping Huang;Dazhuang Wang;Peiling Liang;Shaofang Ren;Xuesong Hu;Yewen Qin;Wei Ke;Ralf Jauch;Andrew Paul Hutchins;Mei Wang;Fuchou Tang;Xiao-Yang Zhao

作者机构:State Key Laboratory of Organ Failure ResearchDepartment of Developmental BiologySchool of Basic Medical SciencesSouthem Medical UniversityGuangzhou 510515China Beijing Advanced Innovation Center for GenomicsSchool of Life SciencesPeking UniversityBeijing 100871China Biomedical Pioneering Innovation CenterMinistry of Education Key Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Departmentof UrologyNanfang HospitalSouthem Medical UniversityGuangzhou 510515China School of Biomedical SciencesLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina Department of BiologySoutherm University of Science and TechnologyShenzhen 518055China Department of NeonatologyZhujiang HospitalSouthem Medical UniversityGuangzhou 510280China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue EngineeringSouthem Medical UniversityGuangzhou 510515China Department of GynecologyZhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Key Laboratory of Mental Health of the Ministry of EducationGuangzhou 510515China Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)Guangzhou 510005China Department of Plastic SurgeryAffliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China 

出 版 物:《Protein & Cell》 (蛋白质与细胞(英文版))

年 卷 期:2023年第14卷第7期

页      面:479-498页

核心收录:

学科分类:0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基  金:supported by grants from the National Key R&D Program of China(2020YFA0113300 to M.W.,2018YFA0107601 to F.T.,2019YFA0801802 to M.W.,2022YFA0806300 to X.-Y.Z.) the National Natural Science Foundation of China(82071711 to X.-Y.Z.,32170866 to M.W.,U22A20278 to X.-Y.Z.) Key Research&Development Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(2018GZR110104002 to X.-Y.Z.) Guangdong Basic and Applied Basic Research Foundation(2021A1515010802 to M.W.) National Demonstration Center for Experimental Education of Basic Medical Sciences(Southerm Medical University) 

主  题:reprogramming spermatogonial stem cell tetraploid complementation imprinting 

摘      要:Although somatic cells can be reprogrammed to pluripotent stem cells(PsCs)with pure chemicals,authentic pluripotency of chemically induced pluripotent stem celis(CipsCs)has never been achieved through tetraploid complementation *** reprogramming of spermatogonial stem cells(ssCs)was another non-transgenic way to obtain PsCs,but this process lacks mechanistic ***,we reconstructed the trajectory of mouse SsC reprogramming and developed a five-chemical combination,boosting the reprogramming effciency by nearly 80-to *** importantly,chemical induced germline-derived PsCs(5C-gPSCs),but not gpsCs and chemical induced pluripotent stem cells,had authentic pluripotency,as determined by tetraploid ***,ssCs traversed through an inverted pathway of in vivo germ ceil development,exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to ***,ssC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5c-gPsCs,which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both *** work sheds ight on the unique regulatory network underpinning SsC reprogramming,providing insights to understand generic mechanisms for cell-fate decision and epigenetic-relateddisorders in regenerative medicine.

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