Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily pene...Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin,and be absorbed into the bloodstream.Here,we employed a human embryonic stem cell(h ESC)-based differentiation system towards keratinocytes,to test the effects of ultrafine carbon particles,which mimic ambient ultrafine particles,at environment related concentrations.We found that10 ng/mL to 10μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in h ESCs.Moreover,1μg/mL to 10μg/mL carbon particle treatments disrupted the keratinocyte differentiation,and up-regulated inflammationand psoriasis-related genes,such as IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,CXCL8,and S100 A7 and S100 A9,respectively.Overall,our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.展开更多
The stem cells of an organism only possess extraordinary capacity to change into different cell types during the early life and growth of an organism. When these stem cells divide into different new cells, these eithe...The stem cells of an organism only possess extraordinary capacity to change into different cell types during the early life and growth of an organism. When these stem cells divide into different new cells, these either remain as stem cells or develop to become other cells with specialized function. For this reason, stem cells offer direct relevance to human health, as theoretically, using stem cell technology, different organs are expected to be regenerated. To this, the Human Embryonic Stem Cells (HESCs) are natural pluripotent cell, but ethical issues covering many countries have put research work on a bit back-foot. However, the Induced Pluripotent Stem Cells (iPSCs) technology has completely revitalized the world to use this technology universally and it therefore seems that more research on this technology will surely be of enormous help in public health. In addition, application of the stem cell technology in personalized-medicine has been started recently. In this concern, the stem cell banking facilities have provided new avenues for preserving the cord blood of the new-borne child and treat them in future by using her/his own preserved stem cells. However, like all new technologies, the output from stem cell research requires to be evaluated more closely. Furthermore, with proper guidelines on ethical issues and extended research following these strategies, the stem cell technology is expected to not only be of huge benefit to human health, but also the benefit can be extended to the survival of endangered animals as well.展开更多
As a critical tumor suppressor, p53 is inactivated in human cancer cells by somatic gene mutation or disruption of pathways required for its activation. Therefore, it is critical to elucidate the mechanism underlying ...As a critical tumor suppressor, p53 is inactivated in human cancer cells by somatic gene mutation or disruption of pathways required for its activation. Therefore, it is critical to elucidate the mechanism underlying p53 activation after genotoxic and cellular stresses. Accumulating evidence has indicated the importance of posttranslational modifications such as acetylation in regulating p53 stability and activity. However, the physiological roles of the eight identified acetylation events in regulating p53 responses remain to be fully understood. By employing homologous recombination, we introduced various combinations of missense mutations （lysine to arginine） into eight acetylation sites of the endogenous p53 gene in human embryonic stem cells （hESCs）. By determining the p53 responses to DNA damage in the p53 knock-in mutant hESCs and their derivatives, we demonstrate physiological importance of the acetylation events within the core domain （Kt20 and K164） and at the C-terminus （K370/372/373/381/382/ 386） in regulating human p53 responses to DNA damage.展开更多
基金supported by the National Natural Science Foundation of China(Nos.21876197,21577166,21707160)the Chinese Academy of Sciences(Nos.XDB14040301,QYZDJSSW-DQC017)the K.C.Wong Education Foundation
文摘Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin,and be absorbed into the bloodstream.Here,we employed a human embryonic stem cell(h ESC)-based differentiation system towards keratinocytes,to test the effects of ultrafine carbon particles,which mimic ambient ultrafine particles,at environment related concentrations.We found that10 ng/mL to 10μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in h ESCs.Moreover,1μg/mL to 10μg/mL carbon particle treatments disrupted the keratinocyte differentiation,and up-regulated inflammationand psoriasis-related genes,such as IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,CXCL8,and S100 A7 and S100 A9,respectively.Overall,our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.
文摘The stem cells of an organism only possess extraordinary capacity to change into different cell types during the early life and growth of an organism. When these stem cells divide into different new cells, these either remain as stem cells or develop to become other cells with specialized function. For this reason, stem cells offer direct relevance to human health, as theoretically, using stem cell technology, different organs are expected to be regenerated. To this, the Human Embryonic Stem Cells (HESCs) are natural pluripotent cell, but ethical issues covering many countries have put research work on a bit back-foot. However, the Induced Pluripotent Stem Cells (iPSCs) technology has completely revitalized the world to use this technology universally and it therefore seems that more research on this technology will surely be of enormous help in public health. In addition, application of the stem cell technology in personalized-medicine has been started recently. In this concern, the stem cell banking facilities have provided new avenues for preserving the cord blood of the new-borne child and treat them in future by using her/his own preserved stem cells. However, like all new technologies, the output from stem cell research requires to be evaluated more closely. Furthermore, with proper guidelines on ethical issues and extended research following these strategies, the stem cell technology is expected to not only be of huge benefit to human health, but also the benefit can be extended to the survival of endangered animals as well.
基金This work was supported by grants from California Institute for Regenerative Medicine （RC1-00148） to Y.X. and grants from the National Natural Science Foundation of China （Grant Nos. 81172828 and 81373166） to X.F.
文摘As a critical tumor suppressor, p53 is inactivated in human cancer cells by somatic gene mutation or disruption of pathways required for its activation. Therefore, it is critical to elucidate the mechanism underlying p53 activation after genotoxic and cellular stresses. Accumulating evidence has indicated the importance of posttranslational modifications such as acetylation in regulating p53 stability and activity. However, the physiological roles of the eight identified acetylation events in regulating p53 responses remain to be fully understood. By employing homologous recombination, we introduced various combinations of missense mutations （lysine to arginine） into eight acetylation sites of the endogenous p53 gene in human embryonic stem cells （hESCs）. By determining the p53 responses to DNA damage in the p53 knock-in mutant hESCs and their derivatives, we demonstrate physiological importance of the acetylation events within the core domain （Kt20 and K164） and at the C-terminus （K370/372/373/381/382/ 386） in regulating human p53 responses to DNA damage.
