据Genovese P 2014年6月12日[Nature,2014,510（7604）：235-240.]报道,意大利San Raffaele科学研究所的研究人员在人类造血干细胞（HSC）突破性地实现了靶向基因组编辑。基因治疗为一些因基因缺陷引起的遗传性疾病提供了良好的治疗效...据Genovese P 2014年6月12日[Nature,2014,510（7604）：235-240.]报道,意大利San Raffaele科学研究所的研究人员在人类造血干细胞（HSC）突破性地实现了靶向基因组编辑。基因治疗为一些因基因缺陷引起的遗传性疾病提供了良好的治疗效果。然而传统的方法是采用一种遗传工程载体将突变基因的一个功能拷贝传送到病变细胞添加到基因组中。尽管更为先进的载体,例如慢病毒载体证实提高了安全性和疗效,利用半随机插入载体存在的插入突变及失控性转基因表达风险仍然令人们感到担忧。这些不良效应有可能会触发癌症形成、展开更多
Recombinant human-salmon calcxtonin （hsCT） was synthesized and expressea on the cell surtaces ot recombinant Saccharomyces cerevisiae （yAGA2-hsCT） using the pAGA2-hsCT expression vector. Expression of recombinant ...Recombinant human-salmon calcxtonin （hsCT） was synthesized and expressea on the cell surtaces ot recombinant Saccharomyces cerevisiae （yAGA2-hsCT） using the pAGA2-hsCT expression vector. Expression of recombinant hsCT was verified by flow cytometer.The resorption activity of osteoclasts was inhibited by recombinant hsCT protein which released from the cell surface of yAGA2-hsCT. Blood calcium determination in rats showed the activity of yAGA2-hsCT following oral administration of 5 mg/kg lyophilized transformant yeast to hypercalcemia rats decreases the serum calcium from 2.82 ±0.023 mM to 2.662 ± 0.012 mM.展开更多
RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lin...RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.展开更多
Congenital human cytomegalovirus(HCMV) infection is a leading infectious cause of birth defects.Previous studies have reported birth defects with multiple organ maldevelopment in congenital HCMV-infected neonates. Mul...Congenital human cytomegalovirus(HCMV) infection is a leading infectious cause of birth defects.Previous studies have reported birth defects with multiple organ maldevelopment in congenital HCMV-infected neonates. Multipotent mesenchymal stromal cells(MSCs) are a group of stem/progenitor cells that are multi-potent and can self-renew, and they play a vital role in multiorgan formation. Whether MSCs are susceptible to HCMV infection is unclear. In this study, MSCs were isolated from Wharton's jelly of the human umbilical cord and identified by their plastic adherence, surface marker pattern, and differentiation capacity. Then, the MSCs were infected with the HCMV Towne strain, and infection status was assessed via determination of viral entry,replication initiation, viral protein expression, and infectious virion release using western blotting,immunofluorescence assays, and plaque forming assays. The results indicate that the isolated MSCs were fully permissive for HCMV infection and provide a preliminary basis for understanding the pathogenesis of HCMV infection in non-nervous system diseases, including multi-organ malformation during fetal development.展开更多
文摘据Genovese P 2014年6月12日[Nature,2014,510（7604）：235-240.]报道,意大利San Raffaele科学研究所的研究人员在人类造血干细胞（HSC）突破性地实现了靶向基因组编辑。基因治疗为一些因基因缺陷引起的遗传性疾病提供了良好的治疗效果。然而传统的方法是采用一种遗传工程载体将突变基因的一个功能拷贝传送到病变细胞添加到基因组中。尽管更为先进的载体,例如慢病毒载体证实提高了安全性和疗效,利用半随机插入载体存在的插入突变及失控性转基因表达风险仍然令人们感到担忧。这些不良效应有可能会触发癌症形成、
文摘Recombinant human-salmon calcxtonin （hsCT） was synthesized and expressea on the cell surtaces ot recombinant Saccharomyces cerevisiae （yAGA2-hsCT） using the pAGA2-hsCT expression vector. Expression of recombinant hsCT was verified by flow cytometer.The resorption activity of osteoclasts was inhibited by recombinant hsCT protein which released from the cell surface of yAGA2-hsCT. Blood calcium determination in rats showed the activity of yAGA2-hsCT following oral administration of 5 mg/kg lyophilized transformant yeast to hypercalcemia rats decreases the serum calcium from 2.82 ±0.023 mM to 2.662 ± 0.012 mM.
基金This work was supported by the National Program on Key Basic Research Project of China （973 Program 2015CB964902）, the National Natural Science Foundation of China （NSFC H81170466 and H81370597）, and the CAMS Initiatives for Innovative Medicine （2016-12M-1-018） awarded to F.M.
文摘RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.
基金supported by the National Science Foundation of China (81071350,81271850,and 31170155)the National Program on Key Basic Research Project (973 program 2011CB504804 and 2012CB519003)
文摘Congenital human cytomegalovirus(HCMV) infection is a leading infectious cause of birth defects.Previous studies have reported birth defects with multiple organ maldevelopment in congenital HCMV-infected neonates. Multipotent mesenchymal stromal cells(MSCs) are a group of stem/progenitor cells that are multi-potent and can self-renew, and they play a vital role in multiorgan formation. Whether MSCs are susceptible to HCMV infection is unclear. In this study, MSCs were isolated from Wharton's jelly of the human umbilical cord and identified by their plastic adherence, surface marker pattern, and differentiation capacity. Then, the MSCs were infected with the HCMV Towne strain, and infection status was assessed via determination of viral entry,replication initiation, viral protein expression, and infectious virion release using western blotting,immunofluorescence assays, and plaque forming assays. The results indicate that the isolated MSCs were fully permissive for HCMV infection and provide a preliminary basis for understanding the pathogenesis of HCMV infection in non-nervous system diseases, including multi-organ malformation during fetal development.
