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

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. Multipotent mesenchymal stem cells (M-MSCs) derived from human embryonic stem cells (H9) were maintained in the absence (AG_0) or presence of 250 ug/ml (0.74 mM; AA250) for 3 days. Total RNA from three independent replicates was isolated using the RNeasy Mini Kit (QIAGEN, Valencia, CA), including treatment with DNase I (QIAGEN). One ug of total RNA was used for the Affymetrix GeneChip Human 2.0 ST Array (Affymetrix, Santa Clara, CA), in accordance with the manufacturer’s instructions.