The discovery of induced pluripotent stem cells (iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; howe...The discovery of induced pluripotent stem cells (iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs (HiPSCs) remains to be fully elucidated. Here, we evaluated the malignant potential of HiPSCs by using both colony formation assays and tumorigenicity tests. We demonstrated that HiPSCs formed tumorigenic colonies when grown in cancer cell culture medium and produced malignancies in immunodeficient mice. Furthermore, we analyzed genomic instability in HiPSCs using whole-genome copy number variation analysis and determined that the extent of genomic instability was related with both the cells′ propensity to form colonies and their potential for tumorigenesis. These findings indicate a risk for potential malignancy of HiPSCs derived from genomic instability and suggest that quality control tests, including comprehensive tumorigenicity assays and genomic integrity validation, should be rigorously executed before the clinical application of HiPSCs. In addition, HiPSCs should be generated through the use of combined factors or other approaches that decrease the likelihood of genomic instability.展开更多
Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem(i PS) cells from mouse mature adipocytes by forced expression of six transcription f...Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem(i PS) cells from mouse mature adipocytes by forced expression of six transcription factors(Oct4, Sox2, c-Myc, Klf4, Rarc, and Lrh1) with a piggy Bac transposon-based strategy. The resulting i PS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1,and remained pluripotent on a 2i media. In vitro differentiation of the i PS cells showed that the cell derivatives of all three germ layers could be readily obtained through formation of embryoid bodies. Most importantly, these adipocytederived i PS cells were capable of producing chimera with high frequencies when reintroduced into early-stage embryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming technology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.展开更多
A novel coronavirus disease 2019(COVID-19)emerged around December 2019 in Wuhan,China and has spread rapidly worldwide(Lu et al.,2020).Until March 27,2020,the Chinese health authorities had reported 82082 confirmed CO...A novel coronavirus disease 2019(COVID-19)emerged around December 2019 in Wuhan,China and has spread rapidly worldwide(Lu et al.,2020).Until March 27,2020,the Chinese health authorities had reported 82082 confirmed COVID-19 cases in China with 3298 deaths and 381443 confirmed cases with 20787 deaths outside China.The World Health Organization(WHO)named the virus SARS-CoV-2,which belongs to a distinct clade from the human severe acute respiratory syndrome CoV(SARS-CoV)and Middle East respiratory syndrome CoV(MERSCoV)(Zhu et al.,2020).展开更多
Background:Sorting nexins are a large family of proteins that are associated with various components of the endosome system and they play many roles in processes such as endocytosis,intracellular protein trafficking a...Background:Sorting nexins are a large family of proteins that are associated with various components of the endosome system and they play many roles in processes such as endocytosis,intracellular protein trafficking and cell signaling.The subcellular distribution patterns of many of them remain controversial and their in vivo functions have not been characterized yet.Results:We investigated the subcellular distribution and function of SNX16 in this study.SNX16 is detected on Rab5-positive endosomes localized adjacent to focal adhesions at cell cortex.Inhibition of SNX23,polymerization of microtubule filaments as well as the PI3-kinase all disrupt the cell cortex distribution of SNX16.Ectopic expression of SNX16 reduces the migration and the tumor formation activity of MCF-7 cells.Conclusion:Our results indicate that,in addition to the PI3P,there is a SNX23-and microtubule-dependent cargo transport pathway required for the proper subcellular distribution of SNX16.SNX16 plays a negative regulatory role during cell migration and tumorigenesis.展开更多
基金supported by grants from the Chinese National 973 Program (No.2006CB910104 and No.2010CB912201)the Chinese National 863 Program (No.2006AA02A404)+1 种基金the Guangdong Province-National Natural Science Foundation of China Cooperation Program (No.u0732005)Ministry of Education of China (the academic award for excellent doctoral student,2010)
文摘The discovery of induced pluripotent stem cells (iPSCs) is a promising advancement in the field of regenerative medicine. Previous studies have indicated that the teratoma-forming propensity of iPSCs is variable; however, the relationship between tumorigenic potential and genomic instability in human iPSCs (HiPSCs) remains to be fully elucidated. Here, we evaluated the malignant potential of HiPSCs by using both colony formation assays and tumorigenicity tests. We demonstrated that HiPSCs formed tumorigenic colonies when grown in cancer cell culture medium and produced malignancies in immunodeficient mice. Furthermore, we analyzed genomic instability in HiPSCs using whole-genome copy number variation analysis and determined that the extent of genomic instability was related with both the cells′ propensity to form colonies and their potential for tumorigenesis. These findings indicate a risk for potential malignancy of HiPSCs derived from genomic instability and suggest that quality control tests, including comprehensive tumorigenicity assays and genomic integrity validation, should be rigorously executed before the clinical application of HiPSCs. In addition, HiPSCs should be generated through the use of combined factors or other approaches that decrease the likelihood of genomic instability.
基金supported by the National Key Research and Development Program of China Stem Cell and Translational Research,China(2017YFA0104800)the Research Funds from Health@InnoHK Program launched by Innovation Technology Commission of the Hong Kong SAR,China+4 种基金National Natural Science Foundation of China(81570944 and 92068201)Science and Technology Planning Project of Guangdong Province,China(2020B1212060052)High-level Hospital Construction Project(DFJHBF202110)Youth Innovation Promotion of the Chinese Academy of Sciences(2019348)Guangzhou Key Medical Disciplines(2021–2023)。
基金supported in part by the National Basic Research Program of China(2011CB504004,2010CB945500)the Strategic Program of Stem Cell(XDA01020303)+1 种基金the Knowledge Innovation Program of the Chinese Academy of Sciencesthe National Natural Science Foundation of China(90813033)as well as The Guangdong Key High-end Foreign Experts Program Fund
文摘Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem(i PS) cells from mouse mature adipocytes by forced expression of six transcription factors(Oct4, Sox2, c-Myc, Klf4, Rarc, and Lrh1) with a piggy Bac transposon-based strategy. The resulting i PS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1,and remained pluripotent on a 2i media. In vitro differentiation of the i PS cells showed that the cell derivatives of all three germ layers could be readily obtained through formation of embryoid bodies. Most importantly, these adipocytederived i PS cells were capable of producing chimera with high frequencies when reintroduced into early-stage embryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming technology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.
基金This work was supported by the Natural Science Foundation of Guangdong Province(2018A030313652)the National Mega Project on Major Infectious Disease Prevention(2017ZX10103011).
文摘A novel coronavirus disease 2019(COVID-19)emerged around December 2019 in Wuhan,China and has spread rapidly worldwide(Lu et al.,2020).Until March 27,2020,the Chinese health authorities had reported 82082 confirmed COVID-19 cases in China with 3298 deaths and 381443 confirmed cases with 20787 deaths outside China.The World Health Organization(WHO)named the virus SARS-CoV-2,which belongs to a distinct clade from the human severe acute respiratory syndrome CoV(SARS-CoV)and Middle East respiratory syndrome CoV(MERSCoV)(Zhu et al.,2020).
基金We thank members of the lab for technical assistance and helpful discussions.This work was supported by grants from the"Strategic Priority Research Program"of the Chinese Academy of Sciences(XDA01020401,XDA01020307)National Natural Science Foundation of China(31271502)Science and Technology Planning Project of Guangdong Province(2011A060901019).
文摘Background:Sorting nexins are a large family of proteins that are associated with various components of the endosome system and they play many roles in processes such as endocytosis,intracellular protein trafficking and cell signaling.The subcellular distribution patterns of many of them remain controversial and their in vivo functions have not been characterized yet.Results:We investigated the subcellular distribution and function of SNX16 in this study.SNX16 is detected on Rab5-positive endosomes localized adjacent to focal adhesions at cell cortex.Inhibition of SNX23,polymerization of microtubule filaments as well as the PI3-kinase all disrupt the cell cortex distribution of SNX16.Ectopic expression of SNX16 reduces the migration and the tumor formation activity of MCF-7 cells.Conclusion:Our results indicate that,in addition to the PI3P,there is a SNX23-and microtubule-dependent cargo transport pathway required for the proper subcellular distribution of SNX16.SNX16 plays a negative regulatory role during cell migration and tumorigenesis.
