Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174050 | ENA |
REPOSITORIES: ENA
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Project description:The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11) could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. Importantly, the increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G. We also identified a novel OCT4 downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. This small molecule-based stabilization of synthetic mRNA expression may have multiple applications for future cell-based research and therapeutics. 4 samples (untreated H9 hESCs, untreated HUF1 skin fibroblasts, HUF1 cells treated with OCT4 synthetic mRNA, HUF1 cells treated with OCT4 synthetic mRNA and BAY11) were analyzed with 2 biological replicates per sample.
2012-08-29 | E-GEOD-40444 | biostudies-arrayexpress
Project description:The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11) could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. Importantly, the increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G. We also identified a novel OCT4 downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. This small molecule-based stabilization of synthetic mRNA expression may have multiple applications for future cell-based research and therapeutics.
2012-08-29 | GSE40444 | GEO
Project description:The goal of this study is to identify the role of OCT4 in combination with small molecules as the critical cue governing the reprogramming of human somatic cells into OPCs using ChIP-seq
2019-05-02 | GSE130565 | GEO
Project description:Long-term maintenance of functional primary human hepatocytes using small molecules
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Project description:Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules
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Project description:Primary outcome(s): Relationship with mRNA expression of B7 family molecules in blood of patients with colorectal cancer and clinicopathological factors
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Project description:Microbes are fascinating molecular machines which can be equipped with synthetic genetic programs that allow them to produce therapeutic molecules targeted on demand upon disease sensing. Cutibacterium acnes engraftment capacity and its living habitat close to important pharmacological targets makes it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium, the most abundant commensal of the human skin, to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin in vivo, known to modulate cutaneous sebum production.
2023-11-10 | PXD044802 | Pride
Project description:High-throughput sequencing of small RNAs from Xenopus tropicalis (adult liver, adult skin, oocytes stage I, II, III, IV, V, VI). total RNA, ~18-42 nt RNAs isolated using PAGE, ligation to adapters requires 5' monophosphate and 3' OH Illumina/Solexa sequencing of adult liver, adult skin, oocytes stage I, II, III, IV, V, VI
2009-07-09 | E-GEOD-14952 | biostudies-arrayexpress
Project description:Replacing the transcription factor OCT4, one of the master pluripotency regulators, by small molecules has been a long standing challenge to establish small molecule based reprogramming for the generation of human chemically induced pluripotent stem cells (hciPSCs). Using a cell-based high throughput screen, we have previously identified a new series of OCT4-inducing compounds (O4Is). In this paper, we prepared metabolically stable analogues, including O4I4, which strongly activate pluripotency-associated signaling. In combination with a transcription factor cocktail of SOX2, KLF4, MYC, and LIN28 (collectively referred to as CSKML) we achieved to reprogram human fibroblasts into a stable and authentic pluripotent state independent of exogenous OCT4. Transcriptomic analysis of fibroblasts reprogrammed by this approach revealed that O4I4 activated bone morphogenetic protein (BMP)/SMAD/ID signaling at the early stage of reprogramming and subsequent expression of the chromatin modifier, high mobility group A1 (HMGA1), resulting in re-activation of endogenous OCT4 to initiate the reprogramming process. Consistently, chemical or genetic inhibition of BMP/SMAD/ID or HMGA1 was found to block cellular reprogramming. In C.elegans and Drosophila, O4I4 expanded life spans in a BMP-signaling pathway-dependent manner. Given limitations of OCT4-based reprogramming, our findings provide an alternative to OSKM-mediated iPSC generation, and importantly unravel previously-unrecognized molecular mechanisms of pluripotency in the context of regenerative medicine and rejuvenation therapy.
2022-04-06 | GSE200136 | GEO
Project description:Embryonic stem cells (ESCs) of mice and humans have distinct molecular and biological characteristics, raising the question whether an earlier ‘naive’ state of pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support autonomous self-renewal of naive human ESCs based on maintenance of endogenous OCT4 distal enhancer activity, a molecular signature of ground state pluripotency. Iterative chemical screening identified a combination of five kinase inhibitors that induces and maintains OCT4 distal enhancer activity when applied directly to conventional human ESCs. These inhibitors generate a homogeneous population of human pluripotent stem cells in which transcription factors associated with the ground state of pluripotency are highly upregulated. Comparison with previously reported naive human ESCs indicates that our kinase inhibitor cocktail captures a novel pluripotent state in humans that closely resembles mouse ESCs. ChIP-seq data from human embryonic stem cells in naive and primed conditions were generated by deep sequencing using Illumina Hi-Seq 2000.
2014-07-16 | E-GEOD-59434 | biostudies-arrayexpress