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Transcriptome data from ascorbic acid 2-glucose (AA2G) treated human embryonic stem cell vs. non treated human embryonic stem cell

ABSTRACT: Naive or primitive states of stem cells (SCs) resided in specific niches are unstable and difficult to stabilized in vitro. Vitamin-C (VitC), more than suppressing oxygen radicals, exerts the pleiotropic effects on primitive SC functions through various mechanisms. However, instability and unfavorable cellular toxicity by liable oxidation present crucial pitfalls in its reliable application. Here, we show that a VitC derivate, ascorbic acid 2-glucoside (AA2G), without cellular toxicity, stably induces naïve or primitive status of embryonic (ESCs), inducible pluripotent (iPSCs), and mesenchymal SCs (MSCs). AA2G supplement recapitulated the well-known mechanisms of VitC including promoting TET dependent DNA demethylation in murine ESCs or suppressing p53 in iPSCs generation. Particularly, activation of cAMP responsive element binding protein-1 (CREB1) pathway was commonly involved in AA2G potency of ESCs, iPSCs, and MSCs. Importantly, MSCs maintained with AA2G supplement increased the therapeutic outcomes in an asthma mouse model by enhancing their self-renewal, anti-inflammatory, and engraftment capacity. Thus, this study demonstrates that AA2G supplement should be of broad utility to provide an environment supporting naïve pluripotent or primitive state of several types of SCs which critically influences their developmental potency and also efficacy of therapeutic applications.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106183 | GEO | 2019/11/18

REPOSITORIES: GEO

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Transcriptome data from ascorbic acid 2-glucose (AA2G) treated murine embryonic stem cell vs. non treated murine embryonic stem cell

Project description:Naive or primitive states of stem cells (SCs) resided in specific niches are unstable and difficult to stabilized in vitro. Vitamin-C (VitC), more than suppressing oxygen radicals, exerts the pleiotropic effects on primitive SC functions through various mechanisms. However, instability and unfavorable cellular toxicity by liable oxidation present crucial pitfalls in its reliable application. Here, we show that a VitC derivate, ascorbic acid 2-glucoside (AA2G), without cellular toxicity, stably induces naïve or primitive status of embryonic (ESCs), inducible pluripotent (iPSCs), and mesenchymal SCs (MSCs). AA2G supplement recapitulated the well-known mechanisms of VitC including promoting TET dependent DNA demethylation in murine ESCs or suppressing p53 in iPSCs generation. Particularly, activation of cAMP responsive element binding protein-1 (CREB1) pathway was commonly involved in AA2G potency of ESCs, iPSCs, and MSCs. Importantly, MSCs maintained with AA2G supplement increased the therapeutic outcomes in an asthma mouse model by enhancing their self-renewal, anti-inflammatory, and engraftment capacity. Thus, this study demonstrates that AA2G supplement should be of broad utility to provide an environment supporting naïve pluripotent or primitive state of several types of SCs which critically influences their developmental potency and also efficacy of therapeutic applications.

2019-11-18 | GSE106184 | GEO

Transcriptional profiles by deep sequencing (RNA-seq) of in vivo-generated mouse iPSCs, in vitro-generated mouse iPSCs, and mouse ESCs

Project description:We have generated M-bM-^@M-^\reprogrammableM-bM-^@M-^] transgenic mice that ubiquitously express the four Yamanaka factors in an inducible manner. Transitory induction of the transgene results in multiple teratomas emerging from a variety of organs, thus indicating that full reprogramming into iPSCs can occur in vivo. By performing bone marrow transplant experiments, we demonstrate that both hematopoietic cells, as well as non-hematopoietic cells can be reprogrammed in vivo. Remarkably, reprogrammable mice also present circulating iPSCs in the bloodstream (in vivo-iPSCs) with all the expected properties of bona fide iPSCs. Moreover, in contrast to in vitro-iPSCs or embryonic stem cells (ESCs), in vivo-iPSCs have an increased capacity to undergo trophectoderm lineage differentiation, which suggests that in vivo-iPSCs are more plastic or primitive than in vitro-generated iPSCs or ESCs. 6 clones of in vivo-generated iPSCs, 5 indendent clones of in vitro-generated iPSCs, and 3 clones of established ESCs

2013-09-12 | E-GEOD-48364 | biostudies-arrayexpress

Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation

Project description:Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Here, we show that vitC increases the expression of evolutionarily young LINE-1 (L1) elements in mouse ESCs. We find that TET activity is dispensable for these effects, as and that instead L1 upregulation occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we find no evidence of substantially higher retrotransposition rates, suggesting that downstream mechanisms restrict L1 mobility. Notably, treatment of human ESCs with vitC also increases L1 protein levels, which could impact the genetic and epigenetic stability of human pluripotent stem cells.

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Vitamin C and L-Proline antagonistic effects capture alternative states in the pluripotency continuum [RRBS]

Project description:RRBS analysis identified ~1000 differentially methylated regions (DMRs), distributed throughout all chromosomes Interestingly, the majority of DMRs (77% at day 2 and 96% at day 5) that were hypomethylated in VitC-, were conversely hypermethylated in L-Pro-treated ESCs, thus indicating that VitC and L-Pro modulate methylation at the same DNA regions in an opposite manner. Of note, a high fraction of DMRs (50%) laid in promoters (mostly HCPs) and ~20% in enhancers. Moreover, DMRs-associated genes are highly enriched in genes related to developmental process (p=6,3E-38) and DNA-binding transcriptional regulators (p=9,7E-34). Our findings provide the first evidence that L-Pro availability regulates DNA methylation in ESCs and leads to the hypothesis that the antagonistic effects of VitC and L-Pro on DNA methylation pattern might regulate pluripotency.

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Project description:We have generated “reprogrammable” transgenic mice that ubiquitously express the four Yamanaka factors in an inducible manner. Transitory induction of the transgene results in multiple teratomas emerging from a variety of organs, thus indicating that full reprogramming into iPSCs can occur in vivo. By performing bone marrow transplant experiments, we demonstrate that both hematopoietic cells, as well as non-hematopoietic cells can be reprogrammed in vivo. Remarkably, reprogrammable mice also present circulating iPSCs in the bloodstream (in vivo-iPSCs) with all the expected properties of bona fide iPSCs. Moreover, in contrast to in vitro-iPSCs or embryonic stem cells (ESCs), in vivo-iPSCs have an increased capacity to undergo trophectoderm lineage differentiation, which suggests that in vivo-iPSCs are more plastic or primitive than in vitro-generated iPSCs or ESCs.

2013-09-12 | GSE48364 | GEO

Expression data from neural crest cells and neural crest cell-derived MSCs from human pluripotent stem cells of FOP patients and controls

Project description:NCCs and NCC-derived MSCs were induced from FOP-iPSCs and control iPSCs, and their expresion profiles were compared. Comparison of gene expressions among hiPSCs, hESCs, hNCCs and hNC-MSCs from FOP-iPSCs and control-iPSCs.

2015-09-17 | E-GEOD-61510 | biostudies-arrayexpress

Expression data from trisomy 21 and euploid induced pluripotent stem cell hematopoietic progenitors

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2012-09-24 | GSE35561 | GEO

Differentially expressed (DE) genes analysis in synovial fluid mesenchymal stem cells (SF-MSCs), SF-MSC derived iPSCs and iPSC derived MSCs (iPSC-MSCs)

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Expression data from trisomy 21 and euploid induced pluripotent stem cell hematopoietic progenitors

2012-09-24 | E-GEOD-35561 | biostudies-arrayexpress

Tissue- and Aging-specific DNA-Methylation Patterns are erased in Mesenchymal Stromal Cells derived from Induced Pluripotent Stem Cells. [Expression profiling]

Project description:Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate towards a ground-state and may therefore give rise to more standardized cell preparations. We reprogrammed bone marrow MSCs into iPSCs which were subsequently re-differentiated towards MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. DNA methylation (DNAm) profiles of iPSCs maintained some donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs and MSCs are similar in function but differ in their epigenetic makeup. 8 samples were hybridized to the GeneChip Human Gene 1.0 ST Array (Affymetrix)

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