Similar Datasets
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
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 | GSE106183 | GEO
Project description:Transcriptome data from ascorbic acid 2-glucose treated human or mouse embryonic stem cells
| PRJNA415820 | ENA
Project description:Numerous groups have documented that Ascorbic Acid (AA) promotes cardiomyocyte differentiation from both mouse and human ESCs and iPSCs. AA is now considered indispensable for the routine production of hPSC-cardiomyocytes (CMs) using defined media; however, the mechanisms involved with the inductive process are poorly understood. Using a genetically modified mouse embryonic stem cell (mESC) line containing a dsRED transgene driven by the cardiac-restricted portion of the ncx1 promoter, we show that AA promoted differentiation of mESCs to CMs in a dose- and time-dependent manner. Treatment of mPSCs with AA did not modulate total SMAD content; however, the phosphorylated/active forms of SMAD2 and SMAD1/5/8 were significantly elevated. Co-administration of the SMAD2/3 activator Activin A with AA had no significant effect, but the addition of the nodal co-receptor TDGF1 (Cripto) antagonized AA's cardiomyogenic-promoting ability. AA could also reverse some of the inhibitory effects on cardiomyogenesis of ALK/SMAD2 inhibition by SB431542, a TGF? pathway inhibitor. Treatment with BMP2 and AA strongly amplified the positive cardiomyogenic effects of SMAD1/5/8 in a dose-dependent manner. AA could not, however, rescue dorsomorphin-mediated inhibition of ALK/SMAD1 activity. Using an inducible model system, we found that SMAD1, but not SMAD2, was essential for AA to promote the formation of TNNT2+-CMs. These data firmly demonstrate that BMP receptor-activated SMADs, preferential to TGF? receptor-activated SMADs, are necessary to promote AA stimulated cardiomyogenesis. AA-enhanced cardiomyogenesis thus relies on the ability of AA to modulate the ratio of SMAD signaling among the TGF?-superfamily receptor signaling pathways.
| S-EPMC5726630 | biostudies-literature
Project description:Transcriptome data from ascorbic acid 2-glucose (AA2G) treated human embryonic stem cell vs. non treated human embryonic stem cell
| PRJNA415829 | ENA
Project description:Transcriptome data from ascorbic acid 2-glucose (AA2G) treated murine embryonic stem cell vs. non treated murine embryonic stem cell
| PRJNA415830 | ENA
Project description:We performed cDNA microarrays (Affymetrix Mouse Gene 1.0 ST Chip) to analyze the transcriptome of hematopoietic stem and progenitor cells (HSPCs) from E15.5dpc wild type and Geminin (Gmnn) knockout embryos. Lineage negative cells from embryonic livers were isolated using fluorescence activated cell sorting. RNA samples were used to examine the transcriptional programs regulated by Geminin during embryonic hematopoiesis. The data sets were analyzed using the GeneSpring v12.5 platform (Agilent). The list of differentially expressed genes was filtered in meta-analyses to investigate the molecular basis of the phenotype observed in the knockout embryos, which exhibited defective hematopoiesis and death. The data from this study are related to the research article "Geminin deletion increases the number of fetal hematopoietic stem cells by affecting the expression of key transcription factors" (Karamitros et al., 2015) [1]. The microarray dataset has been deposited at the Gene Expression Omnibus (GEO) under accession GEO: GSE53056.
| S-EPMC4816909 | biostudies-literature
Project description:Haploid embryonic stem cells (haESCs) are derived from the inner cell mass of the haploid blastocyst, containing only one set of chromosomes. Extensive and accurate chromatin remodelling occurs during haESC derivation, but the intrinsic transcriptome profiles and chromatin structure of haESCs have not been fully explored. We profiled the transcriptomes, nucleosome positioning, and key histone modifications of four mouse haESC lines, and compared these profiles with those of other closely-related stem cell lines, MII oocytes, round spermatids, sperm, and mouse embryonic fibroblasts. haESCs had transcriptome profiles closer to those of naïve pluripotent stem cells. Consistent with the one X chromosome in haESCs, Xist was repressed, indicating no X chromosome inactivation. haESCs and ESCs shared a similar global chromatin structure. However, a nucleosome depletion region was identified in 2056 promoters in ESCs, which was absent in haESCs. Furthermore, three characteristic spatial relationships were formed between transcription factor motifs and nucleosomes in both haESCs and ESCs, specifically in the linker region, on the nucleosome central surface, and nucleosome borders. Furthermore, the chromatin state of 4259 enhancers was off in haESCs but active in ESCs. Functional annotation of these enhancers revealed enrichment in regulation of the cell cycle, a predominantly reported mechanism of haESC self-diploidization. Notably, the transcriptome profiles and chromatin structure of haESCs were highly preserved during passaging but different from those of differentiated cell types.
| S-EPMC10472531 | biostudies-literature
Project description:A rare sub-population of mouse embryonic stem cells (mESCs), the 2-cell-like cell, is defined by the expression of MERVL and 2-cell-stage-specific transcript (2C transcript). Here, we report that the ribosomal proteins (RPs) RPL14, RPL18, and RPL23 maintain the identity of mESCs and regulate the expression of 2C transcripts. Disregulation of the RPs induces DUX-dependent expression of 2C transcripts and alters the chromatin landscape. Mechanically, knockdown (KD) of RPs triggers the binding of RPL11 to MDM2, an interaction known to prevent P53 protein degradation. Increased P53 protein upon RP KD further activates its downstream pathways, including DUX. Our study delineates the critical roles of RPs in 2C transcript activation, ascribing a novel function to these essential proteins.
| S-EPMC9968990 | biostudies-literature
Project description:The effects of a histone demethylase inhibitor, GSK-J4, and L-ascorbic acid for the transcriptome in female ES cells were analyzed by RNA-sequence. Total RNA was used for high-throughput sequence with Illumina HiSeq 2500 and mapped to mm10.
2015-05-08 | GSE67674 | GEO