Yamanaka factors （Oct3/4, Sox2, Klf4, c-Myc） are highly expressed in embryonic stem （ES） cells, and their overexpression can induce pluripotency in both mouse and human somatic cells, indicating that these factors...Yamanaka factors （Oct3/4, Sox2, Klf4, c-Myc） are highly expressed in embryonic stem （ES） cells, and their overexpression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency. However, systemic analysis of the signaling pathways regulated by Yamanaka factors has not yet been fully described. In this study, we identified the target promoters of endogenous Yamanaka factors on a whole genome scale using ChIP （chromatin immunoprecipitation）- on-chip in El4.1 mouse ES cells, and we found that these four factors co-occupied 58 promoters. Interestingly, when Oct4 and Sox2 were analyzed as core factors, Klf4 functioned to enhance the core factors for development regulation, whereas c-Myc seemed to play a distinct role in regulating metabolism. The pathway analysis revealed that Yamanaka factors collectively regulate a developmental signaling network composed of 16 developmental signaling pathways, nine of which represent earlier unknown pathways in ES cells, including apoptosis and cellcycle pathways. We further analyzed data from a recent study examining Yamanaka factors in mouse ES ceils. Interestingly, this analysis also revealed 16 developmental signaling pathways, of which 14 pathways overlap with the ones revealed by this study, despite that the target genes and the signaling pathways regulated by each individual Yamanaka factor differ significantly between these two datasets. We suggest that Yamanaka factors critically regulate a developmental signaling network composed of approximately a dozen crucial developmental signaling pathways to maintain the pluripotency of ES cells and probably also to induce pluripotent stem cells.展开更多
The role of Yamanaka factors as the core regulators in the induction of pluripotency during somatic cell reprogramming has been discovered recently. Our previous study found that Yamanaka factors regulate a developmen...The role of Yamanaka factors as the core regulators in the induction of pluripotency during somatic cell reprogramming has been discovered recently. Our previous study found that Yamanaka factors regulate a developmental signaling network in maintaining embryonic stem （ES） cell pluripotency. Here, we established completely reprogrammed induced pluripotent stem （iPS） cells and analyzed the global promoter occupancy of Yamanaka factors in these cells by ChiP-chip assays. We found that promoters of 565 genes were co-bound by four Yamanaka factors in iPS cells, a 10-fold increase when compared with their binding in ES cells. The promoters occupied by a single Yamanaka factor distributed equally in activated and repressed genes in iPS cells, while in ES cells Oct4, Sox2, or KIf4 distributed mostly in repressed genes and c-Myc in activated ones. Pathway analysis of the ChiP-chip data revealed that Yamanaka factors regulated 16 developmental signaling pathways in iPS cells, among which 12 were common and 4 were unique compared to pathways regulated in ES ChiP-chip dataset in iPS cells and observed similar results, cells. We further analyzed another recently published showing the power of ChiP-chip plus pathway analysis for revealing the nature of pluripotency maintenance and regeneration. Next, we experimentally tested one of the repressive signaling pathways and found that its inhibition indeed improved efficiency of cell reprogramming. Taken together, we proposed that there is a core developmental signaling network necessary for pluripotency, with TGF-β, Hedgehog, Wnt, p53 as repressive （Yin） regulators and Jak-STAT, cell cycle, focal adhesion, adherens junction as active （Yang） ones; and Yamanaka factors synergistically regulate them in a Yin-Yang balanced way to induce pluripotency.展开更多
Background:Fetal balloon atrial septoplasty(BAS)is performed through the restrictive foramen ovale in fetal cases with established hypoplastic left heart syndrome(HLHS)and an intact or highly restrictive atrial septum...Background:Fetal balloon atrial septoplasty(BAS)is performed through the restrictive foramen ovale in fetal cases with established hypoplastic left heart syndrome(HLHS)and an intact or highly restrictive atrial septum(RAS).Methods:In the current report,we present a case of high position BAS in a fetus with HLHS/RAS.Results:Echocardiography confirmed an adequate atrial opening above the foramen ovale and fetal pleural effusion resolved spontaneously 1 day after the procedure.Conclusion:To the best of our knowledge,the creation of a high position hole in the thinner part of the atrial septum,instead of the restrictive tiny hole,has not been reported in fetal cases with HLHS/RAS.展开更多
With the increasing scarcity of water resources and growing population,the dual goal of saving irrigation water and increasing grain yield has become a major challenge in rice production around the world.A two-year ly...With the increasing scarcity of water resources and growing population,the dual goal of saving irrigation water and increasing grain yield has become a major challenge in rice production around the world.A two-year lysimetric experiment was conducted to assess the effects of zeolite application(Z_(0):0 and Z1:15 t/hm^(2) and water regimes(W_(0):continuous flooding irrigation,W1:energy-controlled irrigation,W2:alternate wetting and drying irrigation)on grain yield,water use and total nitrogen uptake of rice.Zeolite addition to paddy field significantly increased grain yield,total N uptake,and water use efficiency(WUE),despite a negligible effect on amount of irrigation water used.Compared with W_(0),the separate use of W_(1) and W_(2) each considerably decreased irrigation water.However,W2-grown rice showed a significant decline in grain yield.In contrast,W1 showed comparable grain yield with W_(0),and achieved the highest WUE.Correlation analysis revealed that grain yield was significantly and positively correlated with effective panicles,spikelets per panicle,water consumption,and total N uptake.It is concluded that the combination of zeolite application at the rate of 15 t/hm^(2) and energy-controlled irrigation could be recommended to benefit farmers by reducing irrigation water while improving grain yield on a clay loam soil.展开更多
基金We thank Drs J Zhao, DS Li, L Xiao （Chinese Academy of Sciences, China）, Drs B Leo and H Wang （Agilent Technologies, USA） for helpful discussions and technical assistance, and Drs HK Mei and Y Qiu （GlaxoSmithKline, UK） for the DAVID analysis. This research was supported by the Ministry of Science and Technology （2005CB522406, 2006CB943900, 2007CB947904, 2007CB947100, 2009CB941100, and 2007CB948000）, National Natural Science Foundation of China （30621091, 30625014, 30623003, and 90713047）, Shanghai Municipal Commission for Science and Technology （07PJ14099, 06ZR14098, and 06DZ22032）, and the Chinese Academy of Sciences （KSCX2-YW-R-56 and 2007KIP204）.
文摘Yamanaka factors （Oct3/4, Sox2, Klf4, c-Myc） are highly expressed in embryonic stem （ES） cells, and their overexpression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency. However, systemic analysis of the signaling pathways regulated by Yamanaka factors has not yet been fully described. In this study, we identified the target promoters of endogenous Yamanaka factors on a whole genome scale using ChIP （chromatin immunoprecipitation）- on-chip in El4.1 mouse ES cells, and we found that these four factors co-occupied 58 promoters. Interestingly, when Oct4 and Sox2 were analyzed as core factors, Klf4 functioned to enhance the core factors for development regulation, whereas c-Myc seemed to play a distinct role in regulating metabolism. The pathway analysis revealed that Yamanaka factors collectively regulate a developmental signaling network composed of 16 developmental signaling pathways, nine of which represent earlier unknown pathways in ES cells, including apoptosis and cellcycle pathways. We further analyzed data from a recent study examining Yamanaka factors in mouse ES ceils. Interestingly, this analysis also revealed 16 developmental signaling pathways, of which 14 pathways overlap with the ones revealed by this study, despite that the target genes and the signaling pathways regulated by each individual Yamanaka factor differ significantly between these two datasets. We suggest that Yamanaka factors critically regulate a developmental signaling network composed of approximately a dozen crucial developmental signaling pathways to maintain the pluripotency of ES cells and probably also to induce pluripotent stem cells.
文摘The role of Yamanaka factors as the core regulators in the induction of pluripotency during somatic cell reprogramming has been discovered recently. Our previous study found that Yamanaka factors regulate a developmental signaling network in maintaining embryonic stem （ES） cell pluripotency. Here, we established completely reprogrammed induced pluripotent stem （iPS） cells and analyzed the global promoter occupancy of Yamanaka factors in these cells by ChiP-chip assays. We found that promoters of 565 genes were co-bound by four Yamanaka factors in iPS cells, a 10-fold increase when compared with their binding in ES cells. The promoters occupied by a single Yamanaka factor distributed equally in activated and repressed genes in iPS cells, while in ES cells Oct4, Sox2, or KIf4 distributed mostly in repressed genes and c-Myc in activated ones. Pathway analysis of the ChiP-chip data revealed that Yamanaka factors regulated 16 developmental signaling pathways in iPS cells, among which 12 were common and 4 were unique compared to pathways regulated in ES ChiP-chip dataset in iPS cells and observed similar results, cells. We further analyzed another recently published showing the power of ChiP-chip plus pathway analysis for revealing the nature of pluripotency maintenance and regeneration. Next, we experimentally tested one of the repressive signaling pathways and found that its inhibition indeed improved efficiency of cell reprogramming. Taken together, we proposed that there is a core developmental signaling network necessary for pluripotency, with TGF-β, Hedgehog, Wnt, p53 as repressive （Yin） regulators and Jak-STAT, cell cycle, focal adhesion, adherens junction as active （Yang） ones; and Yamanaka factors synergistically regulate them in a Yin-Yang balanced way to induce pluripotency.
基金supported by grants from National Natural Science Foundation of China(NO 81770316)Mount Tai Scholarship ProjectQingdao Outstanding Health Professional Development Fund(2017)
文摘Background:Fetal balloon atrial septoplasty(BAS)is performed through the restrictive foramen ovale in fetal cases with established hypoplastic left heart syndrome(HLHS)and an intact or highly restrictive atrial septum(RAS).Methods:In the current report,we present a case of high position BAS in a fetus with HLHS/RAS.Results:Echocardiography confirmed an adequate atrial opening above the foramen ovale and fetal pleural effusion resolved spontaneously 1 day after the procedure.Conclusion:To the best of our knowledge,the creation of a high position hole in the thinner part of the atrial septum,instead of the restrictive tiny hole,has not been reported in fetal cases with HLHS/RAS.
基金This study was financially supported by the National Natural Science Foundation of China(51679142,51709173)the Special Fund for Agro-scientific Research in the Public Interest from the Ministry of Agriculture,China(201303125).
文摘With the increasing scarcity of water resources and growing population,the dual goal of saving irrigation water and increasing grain yield has become a major challenge in rice production around the world.A two-year lysimetric experiment was conducted to assess the effects of zeolite application(Z_(0):0 and Z1:15 t/hm^(2) and water regimes(W_(0):continuous flooding irrigation,W1:energy-controlled irrigation,W2:alternate wetting and drying irrigation)on grain yield,water use and total nitrogen uptake of rice.Zeolite addition to paddy field significantly increased grain yield,total N uptake,and water use efficiency(WUE),despite a negligible effect on amount of irrigation water used.Compared with W_(0),the separate use of W_(1) and W_(2) each considerably decreased irrigation water.However,W2-grown rice showed a significant decline in grain yield.In contrast,W1 showed comparable grain yield with W_(0),and achieved the highest WUE.Correlation analysis revealed that grain yield was significantly and positively correlated with effective panicles,spikelets per panicle,water consumption,and total N uptake.It is concluded that the combination of zeolite application at the rate of 15 t/hm^(2) and energy-controlled irrigation could be recommended to benefit farmers by reducing irrigation water while improving grain yield on a clay loam soil.
