目的观察IGF2、H19在原发性肝癌中的表达并了解其意义。方法建立原发性肝癌模型,模型建立后第20周处死小鼠取肝癌及癌旁组织储存于-80℃备用,另取正常小鼠肝脏作对照,用Real time RT-PCR方法检测IGF2、H19 mRNA的变化。结果与对照组比较...目的观察IGF2、H19在原发性肝癌中的表达并了解其意义。方法建立原发性肝癌模型,模型建立后第20周处死小鼠取肝癌及癌旁组织储存于-80℃备用,另取正常小鼠肝脏作对照,用Real time RT-PCR方法检测IGF2、H19 mRNA的变化。结果与对照组比较,IGF2、H19在癌旁及癌组织中的表达都显著增加,在癌组织中增加更为显著P<0.05。结论 IGF2、H19的异常变化与小鼠原发性肝癌的发生发展有关。展开更多
Neural stem cells(NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, h...Neural stem cells(NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with animportant role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging.展开更多
Paternal imprinted genes(H19 and Gtl2)are pivotal for prenatal embryonic development in mice.Nongrowing oocytes and sperm-or oocyte-originated haploid embryonic stem cells(ha ESCs)carrying both H19-DMR(differentially ...Paternal imprinted genes(H19 and Gtl2)are pivotal for prenatal embryonic development in mice.Nongrowing oocytes and sperm-or oocyte-originated haploid embryonic stem cells(ha ESCs)carrying both H19-DMR(differentially DNA-methylated region)and IG(intergenic)-DMR deletions that partially mimic paternal imprinting of H19-Igf2 and Dlk1-Dio3 can be employed as sperm replacement to efficiently support full-term embryonic development.However,how H19-DMR and IG-DMR act together to regulate embryonic development is still largely unknown.Here,using androgenetic ha ESC(AG-ha ESC)-mediated semi-cloned(SC)technology,we showed that paternal H19-DMR and IG-DMR are not essential for pre-implantation development of SC embryos generated through injection of AG-ha ESCs into oocytes.H19-DMR plays critical roles before 12.5 days of gestation while IG-DMR is essential for late-gestation of SC embryos.Interestingly,we found that combined deletions of H19 and H19-DMR can further improve the efficiency of normal development of SC embryos at mid-gestation compared to DKO SC embryos.Transcriptome and histology analyses revealed that H19 and H19-DMR combined deletions rescue the placental defects.Furthermore,we showed that H19,H19-DMR and IG-DMR deletions(TKO)give rise to better prenatal and postnatal embryonic development of SC embryos compared to DKO.Together,our results indicate the temporal regulation of paternal imprinted loci during embryonic development.展开更多
文摘目的观察IGF2、H19在原发性肝癌中的表达并了解其意义。方法建立原发性肝癌模型,模型建立后第20周处死小鼠取肝癌及癌旁组织储存于-80℃备用,另取正常小鼠肝脏作对照,用Real time RT-PCR方法检测IGF2、H19 mRNA的变化。结果与对照组比较,IGF2、H19在癌旁及癌组织中的表达都显著增加,在癌组织中增加更为显著P<0.05。结论 IGF2、H19的异常变化与小鼠原发性肝癌的发生发展有关。
文摘Neural stem cells(NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with animportant role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging.
基金partly supported by the Genome Tagging Project,Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation and grants from the Chinese Academy of Sciences(XDB19010204,OYZDJ-SSW-SMC023 and Facility-based Open Research Program)the National Natural Science Foundation of China(31530048,81672117,31730062,31821004,and31601163)+1 种基金the Ministry of Science and Technology of China(2019YFA0109900)Shanghai Municipal Commission for Science and Technology(16JC1420500,17JC1420102,17JC1400900,and17411954900)
文摘Paternal imprinted genes(H19 and Gtl2)are pivotal for prenatal embryonic development in mice.Nongrowing oocytes and sperm-or oocyte-originated haploid embryonic stem cells(ha ESCs)carrying both H19-DMR(differentially DNA-methylated region)and IG(intergenic)-DMR deletions that partially mimic paternal imprinting of H19-Igf2 and Dlk1-Dio3 can be employed as sperm replacement to efficiently support full-term embryonic development.However,how H19-DMR and IG-DMR act together to regulate embryonic development is still largely unknown.Here,using androgenetic ha ESC(AG-ha ESC)-mediated semi-cloned(SC)technology,we showed that paternal H19-DMR and IG-DMR are not essential for pre-implantation development of SC embryos generated through injection of AG-ha ESCs into oocytes.H19-DMR plays critical roles before 12.5 days of gestation while IG-DMR is essential for late-gestation of SC embryos.Interestingly,we found that combined deletions of H19 and H19-DMR can further improve the efficiency of normal development of SC embryos at mid-gestation compared to DKO SC embryos.Transcriptome and histology analyses revealed that H19 and H19-DMR combined deletions rescue the placental defects.Furthermore,we showed that H19,H19-DMR and IG-DMR deletions(TKO)give rise to better prenatal and postnatal embryonic development of SC embryos compared to DKO.Together,our results indicate the temporal regulation of paternal imprinted loci during embryonic development.
