Project description:Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two murine Neurogenin transcription factors in human induced pluripotent stem cells, and obtained neurons with bipolar morphology in four days at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the transition from stem cell to neuron. These profiles were then analyzed to identify the regulatory networks underlying the differentiation of the neurons. Paired end RNA sequencing of iPS cells (PGP1) at 0, 1, 3, and 4 days post- doxycycline induction of murine NGN1 and NGN2. This was done using an Illumina HiSeq, and reads were aligned to hg19
Project description:Even though proteins are produced from mRNA, the correlation between mRNA levels and protein abundances is moderate in most studies, occasionally attributed to complex post-transcriptional regulation. To address this, we generated a paired transcriptome/proteome time course dataset with 14 time points during Drosophila embryogenesis. Despite a limited mRNA-protein correlation (ρ = 0.54), mathematical models describing protein translation and degradation explain 84% of protein time-courses based on the measured mRNA dynamics without assuming complex post-transcriptional regulation, and allow for classification of most proteins into four distinct regulatory scenarios. By performing an in-depth characterization of the putatively post-transcriptionally regulated genes, we postulated that the RNA-binding protein Hrb98DE is involved in post-transcriptional control of sugar metabolism in early embryogenesis and partially validated this hypothesis using Hrb98DE knockdown. In summary, we present a systems biology framework for the identification of post-transcriptional gene regulation for large-scale time-resolved transcriptome and proteome data.
Project description:Post-transcriptional regulation is crucial to shape gene expression. During the Maternal-to-Zygotic transition (MZT), thousands of maternal transcripts are regulated upon fertili-zation and genome activation. Transcript stability can be influenced by cis-elements and trans-factors, but how these inputs are integrated to determine the overall mRNA stability is unclear. Here, we show that most transcripts are under combinatorial regulation by multiple decay pathways. Characterization of the cis-regulatory motifs revealed that nu-cleotide composition bias characteristic of 3’-UTRs poly-U is associated with mRNA stability. In contrast, miR-430, CCUC, CUGC, elements appeared as the main destabiliz-ing motifs, with miR-430 and UAUUUAU (ARE) sequences causing mRNA deadenyla-tion depending on the activation of the genome. We comprehensively identify RNA-protein interactions across the transcriptome during MZT, and their associated regulatory activity. We find that poly-U binding proteins are preferentially associated with 3’-UTR sequences and stabilizing motifs. Analysis of differentially regulated regions revealed antagonistic sequence contexts for poly-C and poly-U binding proteins that shape protein binding and magnitude of regulation across the transcriptome. Finally, we integrate these regulatory motifs into a machine learning model, able to predict the stability of mRNA reporters in vivo. Our findings reveal how mechanisms of post-transcriptional regulation are coordinated to direct changes in mRNA stability within the early embryo.
Project description:<p>This integrated multi-omics resource delineates the molecular and phenotypic trajectories underlying male morphotype differentiation (Blue Claw [BC], Orange Claw [OC], Small Male [SM]) in <em>macrobrachium rosenbergii</em> during determinative developmental stages (100, 110, and 120 days post-stocking). The dataset comprises paired testicular transcriptomic profiles, hemolymph serum metabolomes, and quantitative morphological trait data (15 key metrics), thereby establishing a holistic framework capturing concurrent gene expression dynamics, metabolic flux alterations, and phenotypic manifestations throughout morphotype specification. The synergistic integration of these multidimensional layers enables mechanistic dissection of regulatory networks governing crustacean growth polymorphism, facilitates identification of heritable biomarkers associated with commercially advantageous morphotypes, and provides foundational insights into arthropod phenotypic plasticity.</p>
2025-08-22 | MTBLS12876 | MetaboLights
Project description:Elucidating microRNA regulatory networks using transcriptional, post-transcriptional and histone modification measurements
Project description:Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination In this dataset, we include the microRNA expression data obtained from the profiling of ribosome/polysome-associated miRNAs and mRNAs in proliferating HL60 cells and in cells induced to differentiate by 1,25-dihydroxyvitamin D3 (VitD3) treatment 18 total samples, 9 from control proliferating HL60 cells and 9 from VitD3-treated HL60 cells
Project description:Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination In this dataset, we include the expression data obtained from the profiling of ribosome/polysome-associated miRNAs and mRNAs in proliferating HL60 cells and in cells induced to differentiate by 1,25-dihydroxyvitamin D3 (VitD3) treatment 18 total samples, 9 from control proliferating HL60 cells and 9 from VitD3-treated HL60 cells