Variation of DNA methylation on the IRX1/2 genes is responsible for the neural differentiation propensity in human induced pluripotent stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA883646 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human induced pluripotent stem cells (hiPSCs) are useful as a tool for reproducing neural development in vitro. However, each hiPSC line has a different ability to differentiate into specific lineages, as known as differentiation propensity, resulting in reduced reproducibility and increased time and cost requirements for research use. To overcome this issue, we searched for predictive signatures of neural differentiation propensity of hiPSCs using DNA methylation which is the main modulator of cellular properties. We obtained 32 lines of hiPSC and its comprehensive DNA methylation data by Infinium MethylationEPIC beadchip. To assess the neural differentiation efficiency of these hiPSCs, we measured the percentage of PAX6-positive cells on day 7 of neural stem cell induction by the dual-SMAD inhibition protocol. Using DNA methylation data of undifferentiated hiPSCs and their measured differentiation efficiency into neural stem cells as the set of data, and HSIC Lasso, a machine learning-based nonlinear feature selection method, we attemted to identify neural differentiation associated differentially methylated sites. Epigenome-wide unsupervised clustering could not distinguish between hiPSCs with varying differentiation efficiency. On the other hand, HSIC Lasso identified 62 probes that can explain the neural differentiation efficiency of hiPSCs. Selected features by HSIC Lasso were particularly enriched within the 3 Mbp on chromosome 5, harboring the IRX2, C5orf38, and IRX1 genes. Within this region, DNA methylation rates were correlated with neural differentiation efficiency particular to female hiPSCs and negatively correlated with gene expression of the IRX1/2 genes. In addition, forced expression of the IRX1/2 genes impaired the neural differentiation ability of hiPSCs. We have shown for the first time that DNA methylation state on the IRX1/2 genes of hiPSCs is predictive biomarker of their ability for neural differentiation. The predictive markers for neural differentiation efficiency identified in this study can be useful for selection of suitable undifferetiated hiPSCs prior to differentiation induction.
2022-09-24 | GSE214021 | GEO
Project description:Human induced pluripotent stem cells (hiPSCs) are useful as a tool for reproducing neural development in vitro. However, each hiPSC line has a different ability to differentiate into specific lineages, as known as differentiation propensity, resulting in reduced reproducibility and increased time and cost requirements for research use. To overcome this issue, we searched for predictive signatures of neural differentiation propensity of hiPSCs using DNA methylation which is the main modulator of cellular properties. We obtained 32 lines of hiPSC and its comprehensive DNA methylation data by Infinium MethylationEPIC beadchip. To assess the neural differentiation efficiency of these hiPSCs, we measured the percentage of PAX6-positive cells on day 7 of neural stem cell induction by the dual-SMAD inhibition protocol. Using DNA methylation data of undifferentiated hiPSCs and their measured differentiation efficiency into neural stem cells as the set of data, and HSIC Lasso, a machine learning-based nonlinear feature selection method, we attemted to identify neural differentiation associated differentially methylated sites. Epigenome-wide unsupervised clustering could not distinguish between hiPSCs with varying differentiation efficiency. On the other hand, HSIC Lasso identified 62 probes that can explain the neural differentiation efficiency of hiPSCs. Selected features by HSIC Lasso were particularly enriched within the 3 Mbp on chromosome 5, harboring the IRX2, C5orf38, and IRX1 genes. Within this region, DNA methylation rates were correlated with neural differentiation efficiency particular to female hiPSCs and negatively correlated with gene expression of the IRX1/2 genes. In addition, forced expression of the IRX1/2 genes impaired the neural differentiation ability of hiPSCs. We have shown for the first time that DNA methylation state on the IRX1/2 genes of hiPSCs is predictive biomarker of their ability for neural differentiation. The predictive markers for neural differentiation efficiency identified in this study can be useful for selection of suitable undifferetiated hiPSCs prior to differentiation induction.
2022-09-24 | GSE214020 | GEO
Project description:Variation of DNA methylation on the IRX1/2 genes is responsible for the neural differentiation propensity in human induced pluripotent stem cells [Illumina Infunium MethylationEPIC]
| PRJNA883656 | ENA
Project description:Variation of DNA methylation on the IRX1/2 genes is responsible for the neural differentiation propensity in human induced pluripotent stem cells [Agilent SurePrint G3 Human GE v3 8x60K Microarray]
| PRJNA883654 | 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.
2011-06-01 | GSE27834 | GEO
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
Project description:In this study, we found evidence of neural conversion of human pluripotent stem cells(hPSCs) to neural stem cells(NSCs) when in a co-cultured state. mRNA sequencing was performed to investigate the factors facilitating neural conversion of hPSCs. Candidate genes responsible for neural conversion were drawn out through GO and DEG analysis. The meaning of this study lies on the possibility of the establishment of a new, fast and efficient NSC differentiation protocol with a reproducible manner across hESC and hiPSC lines.
2019-04-06 | GSE129375 | GEO
Project description:This study examines and compares the protein content in conditioned media collected from neural cell types generated from human pluripotent stem cells. Conditioned media was prepared for 48 hours at a final endpoint of differentiation day 12. Both groups are from parental line WTC11 and cultured as a monolayer on matrigel. Both groups contain a transgene cassette for doxycycline-inducible expression of sox9 and nfia. Doxycycline was only included in the iAstro groups, whereas it was omitted in the neural progenitor cell groups.
2022-01-19 | PXD030821 | Pride
Project description:IntroductionHuman induced pluripotent stem cells (hiPSCs) are useful tools for reproducing neural development in vitro. However, each hiPSC line has a different ability to differentiate into specific lineages, known as differentiation propensity, resulting in reduced reproducibility and increased time and funding requirements for research. To overcome this issue, we searched for predictive signatures of neural differentiation propensity of hiPSCs focusing on DNA methylation, which is the main modulator of cellular properties.MethodsWe obtained 32 hiPSC lines and their comprehensive DNA methylation data using the Infinium MethylationEPIC BeadChip. To assess the neural differentiation efficiency of these hiPSCs, we measured the percentage of neural stem cells on day 7 of induction. Using the DNA methylation data of undifferentiated hiPSCs and their measured differentiation efficiency into neural stem cells as the set of data, and HSIC Lasso, a machine learning-based nonlinear feature selection method, we attempted to identify neural differentiation-associated differentially methylated sites.ResultsEpigenome-wide unsupervised clustering cannot distinguish hiPSCs with varying differentiation efficiencies. In contrast, HSIC Lasso identified 62 CpG sites that could explain the neural differentiation efficiency of hiPSCs. Features selected by HSIC Lasso were particularly enriched within 3 Mbp of chromosome 5, harboring IRX1, IRX2, and C5orf38 genes. Within this region, DNA methylation rates were correlated with neural differentiation efficiency and were negatively correlated with gene expression of the IRX1/2 genes, particularly in female hiPSCs. In addition, forced expression of the IRX1/2 impaired the neural differentiation ability of hiPSCs in both sexes.ConclusionWe for the first time showed that the DNA methylation state of the IRX1/2 genes of hiPSCs is a predictive biomarker of their potential for neural differentiation. The predictive markers for neural differentiation efficiency identified in this study may be useful for the selection of suitable undifferentiated hiPSCs prior to differentiation induction.
| S-EPMC9719094 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-24 | GSE214022 | GEO