The Type I interferon response impairs differentiation potential of pluripotent stem cells [seq]
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PROVIDER: PRJNA506373 | ENA |
REPOSITORIES: ENA
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Project description:The Type I interferon response impairs differentiation potential of pluripotent stem cells
| PRJNA506369 | ENA
Project description:The Type I interferon response impairs differentiation potential of pluripotent stem cells [RT-qPCR]
| PRJNA506372 | ENA
Project description:Upon virus infection, pluripotent stem cells neither induce nor respond to canonical type I interferons (IFN-I). To better understand this biology, we characterized induced pluripotent stem cells (iPSCs) as well as their differentiated parental or rederived counterparts. We confirmed that only iPSCs failed to respond to viral RNA, IFN-I, or viral infection. This lack of response could be phenocopied in fibroblasts with the expression of a reprogramming factor which repressed the capacity to induce canonical antiviral pathways. To ascertain the consequences of restoring the antiviral response in the context of pluripotency, we engineered a system to engage these defenses in iPSCs. Inducible expression of a recombinant virus-activated transcription factor resulted in the successful reconstitution of antiviral defenses through the direct up-regulation of IFN-I-stimulated genes. Induction of the antiviral signature in iPSCs, even for a short duration, resulted in the dysregulation of genes associated with all three germ layers despite maintaining pluripotency markers. Trilineage differentiation of these same cells showed that engagement of the antiviral defenses compromised ectoderm and endoderm formation and dysregulated the development of mesodermal sublineages. In all, these data suggest that the temporal induction of the antiviral response primes iPSCs away from pluripotency and induces numerous aberrant gene products upon differentiation. Together these results suggest that the IFN-I system and pluripotency may be incompatible with each other and thus explain why stem cells do not utilize the canonical antiviral system.
| S-EPMC6347712 | biostudies-literature
Project description:Upon virus infection,pluripotent stem cells neither induce nor respond to canonical Type I interferons (IFN-I). To better understand this biology,we characterized induced pluripotent stem cells (iPSCs) as well as their differentiated parental or re-derived counterparts. We confirmed that only iPSCs failed to respond to viral RNA,Type I interferon (IFN-I),or viral infection. This lack of response could be phenocopied in fibroblasts with the expression of a reprogramming factor which repressed the capacity to induce canonical antiviral pathways. To ascertain the consequences of restoring the antiviral response in the context of pluripotency,we engineered a system to engage these defenses in iPSCs. Inducible expression of a recombinant virus-activated transcription factor resulted in the successful reconstitution of antiviral defenses through the direct upregulation of IFN-I stimulated genes. Induction of the antiviral signature in iPSCs,even for a short duration,resulted in the dysregulation of genes associated with all three germ layers despite maintaining pluripotency markers. Trilineage differentiation of these same cells showed that engagement of the antiviral defenses compromised ectoderm and endoderm formation and dysregulated the development of mesodermal sublineages. In all,these data suggest that the temporal induction of the antiviral response primes iPSCs away from pluripotency and induces numerous aberrant gene products upon differentiaton. Together these results suggest that the IFN-I system and pluripotency may be incompatible with each other and thus explain why stem cells do not utilize the canonical antiviral system.
2018-11-22 | GSE122791 | GEO
Project description:Upon virus infection,pluripotent stem cells neither induce nor respond to canonical Type I interferons (IFN-I). To better understand this biology,we characterized induced pluripotent stem cells (iPSCs) as well as their differentiated parental or re-derived counterparts. We confirmed that only iPSCs failed to respond to viral RNA,Type I interferon (IFN-I),or viral infection. This lack of response could be phenocopied in fibroblasts with the expression of a reprogramming factor which repressed the capacity to induce canonical antiviral pathways. To ascertain the consequences of restoring the antiviral response in the context of pluripotency,we engineered a system to engage these defenses in iPSCs. Inducible expression of a recombinant virus-activated transcription factor resulted in the successful reconstitution of antiviral defenses through the direct upregulation of IFN-I stimulated genes. Induction of the antiviral signature in iPSCs,even for a short duration,resulted in the dysregulation of genes associated with all three germ layers despite maintaining pluripotency markers. Trilineage differentiation of these same cells showed that engagement of the antiviral defenses compromised ectoderm and endoderm formation and dysregulated the development of mesodermal sublineages. In all,these data suggest that the temporal induction of the antiviral response primes iPSCs away from pluripotency and induces numerous aberrant gene products upon differentiaton. Together these results suggest that the IFN-I system and pluripotency may be incompatible with each other and thus explain why stem cells do not utilize the canonical antiviral system.
2018-11-22 | GSE122793 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-11-22 | GSE122794 | GEO
Project description:Lineage-specific differentiation potential varies among different human pluripotent stem cell (hPSC) lines. A stem cell bank may advice researchers on which hPSCs exhibit the highest differentiation potential for a certain lineage. In this study, we aimed at characterizing the hematopoietic differentiation potential from 14 hESC/iPSC lines through the embryoid body (hEB) differentiation system.
2010-07-24 | GSE23091 | GEO
Project description:Lineage-specific differentiation potential varies among different human pluripotent stem cell (hPSC) lines. A stem cell bank may advice researchers on which hPSCs exhibit the highest differentiation potential for a certain lineage. In this study, we aimed at characterizing the hematopoietic differentiation potential from 14 hESC/iPSC lines through the embryoid body (hEB) differentiation system. We carried out gene expression profiling on six different hESC lines grouped according to their ability to differentiate towards hematopoietic lineage: SHEF1, AND1 and H1 were considered as good (high CD45 expression and high CFU potential), whereas H9, HS181 and VAL3 were selected as poor-blood differentiating lines (low CD45 expression and low CFU potential). Human ESC samples were collected during the exponential cell growth phase and stabilized in RNA later. 500 ng of each total RNA sample was labelled with Cy3 using the Quick-Amp Labelling kit and hybridized with the Gene Expression Hybridization kit to a Whole Human Genome Oligo Microarray (Agilent Technologies) following the Manufacturer’s instructions. Each cell line was analyzed as independent duplicates. H9 hESC line was used as the baseline.
2010-07-24 | E-GEOD-23091 | biostudies-arrayexpress
Project description:Elevated p53 Activaties Restrict Differentiation Potential of microRNA-deficient Pluripotent Stem Cells
| PRJNA413063 | ENA
Project description:The use of pluripotent stem cells in regenerative medicine and disease modeling is complicated by the variation in differentiation properties between lines. In this study, we characterized 13 human embryonic stem cell. (hESC) and 26 human induced pluripotent stem cell (hiPSC) lines to identify markers that predict neural differentiation behavior. At a general level, markers previously known to distinguish mouse ESCs from epiblast stem cells (EpiSCs) correlated with neural differentiation behavior. More specifically, quantitative analysis of miR-371-3 expression prospectively identified hESC and hiPSC lines with differential neurogenic differentiation propensity and in vivo dopamine neuron engraftment potential. Transient KLF4 transduction increased miR-371-3 expression and altered neurogenic behavior and pluripotency marker expression. Conversely, suppression of miR- 371-3 expression in KLF4-transduced cells rescued neural differentiation propensity. miR-371-3 expression level therefore appears to have both a predictive and a functional role in determining human pluripotent stem cell neurogenic differentiation behavior. [mRNA profiling (Illumina)]: Four human ESC lines (H9, I4, I6, HUES6) at undifferentiation stages were purified with stem cell surface marker SSEA4 and subjected to RNA extraction and hybridization on Illumina microarrays. Each sample has 3 biological repeats, one of which has two technical repeats. [miRNA profiling (Agilent)]: Four human ESC lines (H9, I4, I6, HUES6) at undifferentiation stages were purified with stem cell surface marker SSEA4 and subjected to RNA extraction and hybridization on Agilent microarrays. Each sample has 3 biological repeats, one of which has two technical repeats.
2011-06-01 | E-GEOD-27834 | biostudies-arrayexpress