scholarly journals Enhanced Immunological Tolerance by HLA-G1 from Neural Progenitor Cells (NPCs) Derived from Human Embryonic Stem Cells (hESCs)

2017 ◽  
Vol 44 (4) ◽  
pp. 1435-1444 ◽  
Author(s):  
Hong-Xi Zhao ◽  
Feng Jiang ◽  
Ya-Jing Zhu ◽  
Li Wang ◽  
Ke Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cells ◽  
Immune Tolerance ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Immunological Tolerance ◽  
Self Renewal ◽  
Hesc Lines

Background: Despite the great potential of utilizing human embryonic stem cells (hESCs)-derived cells as cell source for transplantation, these cells were often rejected during engraftment by the immune system due to adaptive immune response. Methods: We first evaluated HLA-G expression level in both hESCs and differentiated progenitor cells. After that, we generated modified hESC lines that over-express HLA-G1 using lentiviral infection with the construct contains both HLA-G1 and GFP tag. The lentivirus was first produced by co-transfecting HLA-G1 expressing lentiviral vector together with packaging vectors into packaging cell line 293T. Then the produced virus was used for the infection of selected hESC lines. We characterized the generated cell lines phenotype, including pluripotency and self-renewal abilities, as well as immune tolerance ability by mixed lymphocyte reaction (MLR) and cytotoxicity assays. Results: Although the hESCs do not express high levels of HLA-G1, over-expression of HLA-G1 in hESCs still retains their stem cell characteristics as determined by retaining the expression levels of OCT4 and SOX2, two critical transcriptional factors for stem cell function. Furthermore, the HLA-G1 overexpressing hESCs retain the self-renewal and pluripotency characteristics of stem cells, which can differentiate into different types of cells, including pigment cells, smooth muscle cells, epithelia-like cells, and NPCs. After differentiation, the differentiated cells including NPCs retain the high levels of HLA-G1 protein. In comparison with conventional NPCs, these HLA-G1 positive NPCs have enhanced immune tolerance ability. Conclusions: Ectopic expression of HLA-G1, a non-classical major histocompatibility complex class I (MHC I) antigen that was originally discovered involving in engraftment tolerance during pregnancy, can enhance the immunological tolerance in differentiated neural progenitor cells (NPCs). Our study shows that stably overexpressing HLA-G1 in hESCs might be a feasible strategy for enhancing the engraftment of NPCs during transplantation.

scholarly journals SOX1 Is Required for the Specification of Rostral Hindbrain Neural Progenitor Cells from Human Embryonic Stem Cells

iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101475
Author(s):  
Xinyuan Liu ◽  
Zhuoqing Fang ◽  
Jing Wen ◽  
Fan Tang ◽  
Bing Liao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cells ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Neural Progenitor

scholarly journals Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation

Science ◽  
2014 ◽  
Vol 346 (6216) ◽  
pp. 1529-1533 ◽  
Author(s):  
Kosuke Funato ◽  
Tamara Major ◽  
Peter W. Lewis ◽  
C. David Allis ◽  
Viviane Tabar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Cell System ◽  
Genome Wide ◽  
Regulator Genes

Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. The role of the H3.3K27M mutation in tumorigenesis is not fully understood. Here, we use a human embryonic stem cell system to model this tumor. We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice.

BMP Signaling Is Crucial for Regulation Vascular Progenitor Development in Human Embryonic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3037-3037
Author(s):  
Zack Z. Wang ◽  
Hao Bai ◽  
YongXing Gao ◽  
Melanie Arzigian ◽  
Don M. Wojchowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Vascular Cells ◽  
Cd34 Cells ◽  
Vascular Progenitor Cells ◽  
Tgfbeta Signaling

Abstract Abstract 3037 Poster Board II-1013 The generation of vascular cells from pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells, may facilitate tissue transplantation, reperfusion of ischemic tissues, and treatment of pathologies in which endothelial cell dysfunction exists. The signals that direct pluripotent stem cell differentiation into lineage-specific cells remain largely unknown. To identify vascular progenitor cells during hESC differentiation, we characterized various subpopulations that may differentiate into endothelial cells (ECs) and smooth muscle cells (SMCs). In our newly established serum-free medium, hESCs sequentially differentiated into CD34+CD31-, CD34+CD31+, and then CD34-CD31+ cells. Real-time PCR analysis indicated that EC- and SMC-specific genes, including VEGFR2, Tie2, VE-Cad, vWF, SMA, SM22-alpha, calponin, and caldesmon, were expressed significantly high in CD34+CD31+ cells. Furthermore, the CD34+CD31+ cells that were cultured in EC or SMC growth medium had high differentiation potential to become ECs and SMCs. These data suggested that CD34+CD31+ cells contain vascular progenitor cells. By treating hESCs with various factors at different time points, we found that BMP4 was critical to initiate hESC differentiation into CD34+CD31+ progenitor cells, whereas VEGF and FGF2 facilitated CD34+CD31+ cell development in the later stage. Conversely, TGFbeta promoted CD34+CD31- cells that were unable to give rise to ECs and SMCs. In addition, TGFbeta blocked the development of CD34+CD31+ cells induced by BMP4, suggesting that TGFbeta signaling negatively regulates the development of CD34+CD31+ cells during hESC differentiation. DNA microarray analysis indicated that a number of mesodermal genes were increased in BMP4-induced CD34+ cells, and a number of ectodermal genes were increased in TGFbeta-induced CD34+ cells. Therefore, the roles of BMP and TGFbeta signals in lineage differentiation may be inversely reflected in mesoderm and ectoderm. In addition, several pluripotent genes were expressed in TGFbeta-induced CD34+ cells, suggesting that TGFbeta signaling affects maintenance of stem cell pluripotency. The BMP-Smad inhibitor, dorsomorphin, inhibited phosphorylation of Smad1/5/8, and blocked hESC differentiation to CD34+CD31+ progenitor cells, suggesting that BMP Smad-dependent signaling is critical for CD34+CD31+ vascular progenitor development. Our findings provide new insight into how pluripotent hESCs differentiate to generate vascular cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Parinya Noisa ◽  
Taneli Raivio ◽  
Wei Cui
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cells ◽  
Dopaminergic Neurons ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Neural Progenitor

Human embryonic stem cells (hESCs) are able to proliferatein vitroindefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs). hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, includingNURR1, PITX3, andEN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.

scholarly journals Differing Lectin Binding Profiles among Human Embryonic Stem Cells and Derivatives Aid in the Isolation of Neural Progenitor Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23266 ◽  
Author(s):  
Mahesh C. Dodla ◽  
Amber Young ◽  
Alison Venable ◽  
Kowser Hasneen ◽  
Raj R. Rao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cells ◽  
Neural Progenitor Cells ◽  
Lectin Binding ◽  
Embryonic Stem ◽  
Neural Progenitor

scholarly journals Effects of Ionizing Radiation on Self-Renewal and Pluripotency of Human Embryonic Stem Cells

2010 ◽  
Vol 70 (13) ◽  
pp. 5539-5548 ◽  
Author(s):  
Kitchener D. Wilson ◽  
Ning Sun ◽  
Mei Huang ◽  
Wendy Y. Zhang ◽  
Andrew S. Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Ionizing Radiation ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Self Renewal
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