Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD016915
ORGANISM(S): Homo sapiens
PROVIDER: GSE144466 | GEO | 2020/03/09
REPOSITORIES: GEO
Similar Datasets
Project description:The contribution of microRNA-mediated posttranscriptional regulation on the final proteome in differentiating cells remains elusive. Here, we evaluated the impact of microRNAs (miRNAs) on the proteome of human umbilical cord blood-derived unrestricted somatic stem cells (USSC) during retinoic acid (RA) differentiation by a systemic approach using next generation sequencing analysing mRNA and miRNA expression and quantitative mass spectrometry-based proteome analyses. Interestingly, regulation of mRNAs and their dedicated proteins highly correlated during RA-incubation. Additionally, RA-induced USSC demonstrated a clear separation from native USSC thereby shifting from a proliferating to a metabolic phenotype. Bioinformatic integration of up- and downregulated miRNAs and proteins initially implied a strong impact of the miRNome on the XXL-USSC proteome. However, quantitative proteome analysis of the miRNA contribution on the final proteome after ectopic overexpression of downregulated miR-27a-5p and miR-221-5p or inhibition of upregulated miR-34a-5p, respectively, followed by RA-induction revealed only minor proportions of differentially abundant proteins. In addition, only small overlaps of these regulated proteins with inversely abundant proteins in non-transfected RA-treated USSC were observed. Hence, mRNA transcription rather than miRNA-mediated regulation is the driving force for protein regulation upon RA-incubation, strongly suggesting that miRNAs are fine-tuning regulators rather than active primary switches during RA-induction of USSC.
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Project description:Functional analysis of transcriptome (mRNA and microRNA) and proteome formation during treatment of cord-blood derived stem cell lines (USSC) with retinoic acid-containing XXL-medium to estimate the impact of microRNAs on final proteome.
2020-03-09 | GSE144465 | GEO
Project description:Functional analysis of transcriptome (mRNA and microRNA) and proteome formation during treatment of cord-blood derived stem cell lines (USSC) with retinoic acid-containing XXL-medium to estimate the impact of microRNAs on final proteome.
2020-03-09 | GSE144464 | GEO
Project description:Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
| PRJNA603739 | ENA
Project description:Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation [miRNA-Seq]
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Project description:Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation [mRNA-Seq]
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Project description:Plant regeneration via somatic embryogenesis is time-consuming and highly genotype-dependent. The plant somatic embryogenesis process provokes many epigenetics changes including DNA methylation and histone modification. Recently, an elite cotton Jin668, with an extremely high regeneration ability, was developed from its maternal inbred Y668 cultivar using a Successive Regeneration Acclimation (SRA) strategy. To reveal the underlying mechanism of SRA, we carried out a genome-wide single-base resolution methylation analysis for nonembryogenic calluses (NECs), ECs, somatic embryos (SEs) during the somatic embryogenesis procedure and the leaves of regenerated offspring plants. Jin668 (R4) regenerated plants were CHH hypomethylated compared with the R0 regenerated plants of SRA process. The increase in CHH methylation from NEC to EC was demonstrated to be associated with the RNA-dependent DNA methylation (RdDM) and the H3K9me2-dependent pathway. Intriguingly, the hypomethylated CHH differentially methylated regions (DMRs) of promoter activated some hormone-related and WUSCHEL-related homeobox genes during the somatic embryogenesis process. Inhibiting DNA methylation using zebularine treatment in NEC increased the number of embryos. Our multi-omics data provide new insights into the dynamics of DNA methylation during the plant tissue culture and regenerated offspring plants. This study also reveals that induced hypomethylation (SRA) may facilitate the higher plant regeneration ability and optimize maternal genetic cultivar.
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Project description:The self-renewal and differentiation potential of human embryonic stem cells (hESCs) suggests that hESCs could be used for regenerative medicine, especially for restoring neuronal functions in brain diseases. However, the functional properties of neurons derived from hESC are largely unknown. Moreover, because hESCs were derived under diverse conditions, the possibility arises that neurons derived from different hESC lines exhibit distinct properties, but this possibility remains unexplored. To address these issues, we developed a protocol that allows stepwise generation from hESCs of cultures composed of approximately 70-80% human neurons that exhibit spontaneous synaptic network activity. Comparison of neurons derived from the well characterized HSF1 and HSF6 hESC lines revealed that HSF1- but not HSF6-derived neurons exhibit forebrain properties. Accordingly, HSF1-derived neurons initially form primarily GABAergic synaptic networks, whereas HSF6-derived neurons initially form glutamatergic networks. microRNA profiling revealed significant expression differences between the two hESC lines, suggesting that microRNAs may influence their distinct differentiation properties. These observations indicate that although both HSF1 and HSF6 hESCs differentiate into functional neurons, the two hESC lines exhibit distinct differentiation potentials, suggesting that they are preprogrammed. Information on hESC line-specific differentiation biases is crucial for neural stem cell therapy and establishment of novel disease models using hESCs.
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Project description:Embryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data. According to the origins of variation in DNA methylation, we determined the genomic loci associated with allelic-specific methylation or asymmetric DNA methylation, and explored a beta mixture model to infer the genomic loci exhibiting cell-subset specific methylation (CSM). We observed that the putative CSM loci in ESCs are significantly enriched in CpG island (CGI) shelves and regions with histone marks for promoter and enhancer, and the genes hosting putative CSM loci show wide-ranging expression among ESCs. More interestingly, the putative CSM loci may be clustered into co-methylated modules enriching the binding motifs of distinct sets of transcription factors. Taken together, our study provided a novel tool to explore single-cell methylome and transcriptome to reveal the underlying transcriptional regulatory networks associated with epigenetic heterogeneity of ESCs.
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Project description:Salvianolic acids, a group of secondary metabolites produced by Salvia miltiorrhiza, are widely used for treating cerebrovascular diseases. Copper is recognized as a necessary microelement and plays an essential role in plant growth. At present, the effect of copper on the biosynthesis of SalAs is unknown. Here, an integrated metabolomic and transcriptomic approach, coupled with biochemical analyses, was employed to dissect the mechanisms by which copper ions induced the biosynthesis of SalAs. In this study, we identified that a low concentration (5 μM) of copper ions could promote growth of S. miltiorrhiza and the biosynthesis of SalAs. Results of the metabolomics analysis showed that 160 metabolites (90 increased and 70 decreased) were significantly changed in S. miltiorrhiza treated with low concentration of copper ions. The differential metabolites were mainly involved in amino acid metabolism, the pentose phosphate pathway, and carbon fixation in photosynthetic organisms. The contents of chlorophyll a, chlorophyll b, and total chlorophyll were significantly increased in leaves of low concentration of copper-treated S. miltiorrhiza plants. Importantly, core SalA biosynthetic genes (laccases and rosmarinic acid synthase), SalA biosynthesis-related transcription factors (MYBs and zinc finger CCCH domain-containing protein 33), and chloroplast proteins-encoding genes (blue copper protein and chlorophyll-binding protein) were upregulated in the treated samples as indicated by a comprehensive transcriptomic analysis. Bioinformatics and enzyme activity analyses showed that laccase 20 contained copper-binding motifs, and its activity in low concentration of copper ions-treated S. miltiorrhiza was much higher than that in the control. Our results demonstrate that enhancement of copper ions of the accumulation of SalAs might be through regulating laccase 20, MYBs, and zinc finger transcription factors, and photosynthetic genes.
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