Embryonic germ （EG） cells are cultured pluripotent stem cells derived from the primordial germ cells （PGCs） that migrate from the dorsal mesentery of the hindgut to the developing genital ridge. In this study, the...Embryonic germ （EG） cells are cultured pluripotent stem cells derived from the primordial germ cells （PGCs） that migrate from the dorsal mesentery of the hindgut to the developing genital ridge. In this study, the morphology of the porcine genital ridge was assessed in embryos harvested on days 22-30 of pregnancy. PGCs from embryos at these stages were cultured to obtain porcine EG cell lines, and EG-like cells were derived from PGCs from embryos harvested on days 24-28 of pregnancy. The EG-like cells expressed Oct4, Sox2, Nanog, SSEA-3, SSEA-4 and alkaline phosphatase （AP）. These cells were able to form embryoid bodies （EBs） in suspension culture and differentiate into cells representative of the three germ layers as verified by a-fetoprotein （AFP）, s-smooth muscle actin （^-SMA）, and Nestin expression. Spontaneous differentiation from the porcine EG-like cells of delayed passage in vitro showed that they could differentiate into epithelial-like cells, mesenchymal-like cells and neuron-like cells. In vitro directed differentiation generated osteocytes, adipocytes and a variety of neural lineage cells, as demonstrated by alizarin red staining, oil red O staining, and immunoftuorescence for neuronal class III [3-tubulin （Tuj 1）, glial fibrillary protein （GFAP） and galactosylceramidase （GALC）, respectively. These results indicate that porcine EG-like cells have the potential for multi-lineage differentiation and are useful for basic porcine stem cell research.展开更多
Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly m...Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation.The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types.In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases.DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance,proliferation,differentiation and apoptosis by activating or suppressing a number of genes.In most studies,DNA hypermethylation is associated with gene suppression,while hypomethylation or demethylation is associated with gene activation.The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes.However,the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation.In this review,we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work.Furthermore,we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.展开更多
基金supported by the National Basic Research Program of China(Program 973)(Nos.2009CB941002 and 2011CB944202)the Distinguished Young Scholar Foundation of Heilongjiang Province(No.JC200905)
文摘Embryonic germ （EG） cells are cultured pluripotent stem cells derived from the primordial germ cells （PGCs） that migrate from the dorsal mesentery of the hindgut to the developing genital ridge. In this study, the morphology of the porcine genital ridge was assessed in embryos harvested on days 22-30 of pregnancy. PGCs from embryos at these stages were cultured to obtain porcine EG cell lines, and EG-like cells were derived from PGCs from embryos harvested on days 24-28 of pregnancy. The EG-like cells expressed Oct4, Sox2, Nanog, SSEA-3, SSEA-4 and alkaline phosphatase （AP）. These cells were able to form embryoid bodies （EBs） in suspension culture and differentiate into cells representative of the three germ layers as verified by a-fetoprotein （AFP）, s-smooth muscle actin （^-SMA）, and Nestin expression. Spontaneous differentiation from the porcine EG-like cells of delayed passage in vitro showed that they could differentiate into epithelial-like cells, mesenchymal-like cells and neuron-like cells. In vitro directed differentiation generated osteocytes, adipocytes and a variety of neural lineage cells, as demonstrated by alizarin red staining, oil red O staining, and immunoftuorescence for neuronal class III [3-tubulin （Tuj 1）, glial fibrillary protein （GFAP） and galactosylceramidase （GALC）, respectively. These results indicate that porcine EG-like cells have the potential for multi-lineage differentiation and are useful for basic porcine stem cell research.
基金Supported by Beijing Natural Science Foundation,No.7182182the Young Elite Scientist Sponsorship Program by Cast,No.YESS20170089+1 种基金the National Natural Science Foundation of China,No.81600865 and No.81970940the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2018ZX10302207。
文摘Mesenchymal stem cells(MSCs)are a heterogeneous population that can be isolated from various tissues,including bone marrow,adipose tissue,umbilical cord blood,and craniofacial tissue.MSCs have attracted increasingly more attention over the years due to their regenerative capacity and function in immunomodulation.The foundation of tissue regeneration is the potential of cells to differentiate into multiple cell lineages and give rise to multiple tissue types.In addition,the immunoregulatory function of MSCs has provided insights into therapeutic treatments for immune-mediated diseases.DNA methylation and demethylation are important epigenetic mechanisms that have been shown to modulate embryonic stem cell maintenance,proliferation,differentiation and apoptosis by activating or suppressing a number of genes.In most studies,DNA hypermethylation is associated with gene suppression,while hypomethylation or demethylation is associated with gene activation.The dynamic balance of DNA methylation and demethylation is required for normal mammalian development and inhibits the onset of abnormal phenotypes.However,the exact role of DNA methylation and demethylation in MSC-based tissue regeneration and immunomodulation requires further investigation.In this review,we discuss how DNA methylation and demethylation function in multi-lineage cell differentiation and immunomodulation of MSCs based on previously published work.Furthermore,we discuss the implications of the role of DNA methylation and demethylation in MSCs for the treatment of metabolic or immune-related diseases.
