Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA281006 | ENA |
REPOSITORIES: ENA
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Project description:Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition [miRNA]
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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
2014-09-29 | E-GEOD-60548 | biostudies-arrayexpress
Project description:Developmental exposure to environmental toxicants is a cause of skeletal abnormalities. Yet the molecular mechanisms linking early exposure to impaired bone formation remain undefined. Skeletal tissues arise from both neural crest- and mesoderm-derived lineages that rely on shared osteogenic differentiation programs, suggesting that disruption of common regulatory processes may contribute to diverse skeletal outcomes. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene networks and have appeared as indicators of toxicant-induced perturbation. In this study, we examined whether developmentally relevant toxicants are associated with miRNA regulatory networks during osteogenic differentiation. Using a human embryonic stem cell (hESC)-based osteogenic differentiation model, we assessed the effects of nine toxicants spanning distinct primary mechanisms. Toxicant exposure impaired osteogenic differentiation at their IC50, as reflected by altered expression of osteogenic markers and transcriptional remodeling. Global miRNA profiling revealed dysregulation of miRNAs enriched for bone-related biological processes, including regulators of osteogenic commitment and differentiation timing. Integrated miRNA–mRNA network analysis identified a subset of miRNAs linked to core osteogenic and lineage-associated pathways, including RUNX2-dependent transcription and BMP and Wnt signaling. Modulation of representative miRNAs produced osteogenic outcomes consistent with those observed following toxicant exposure and, in some cases, was associated with partial restoration of differentiation in exposed cultures. Collectively, these findings indicate that chemically diverse developmental toxicants are associated with miRNA-mediated regulatory patterns during osteogenic differentiation. Identification of conserved miRNA signatures provides mechanistic insight into developmental bone toxicity and supports the use of miRNA network analysis as a human-relevant endpoint for skeletal hazard identification.
2026-05-31 | GSE324491 | GEO
Project description:Developmental exposure to environmental toxicants is a cause of skeletal abnormalities. Yet the molecular mechanisms linking early exposure to impaired bone formation remain undefined. Skeletal tissues arise from both neural crest- and mesoderm-derived lineages that rely on shared osteogenic differentiation programs, suggesting that disruption of common regulatory processes may contribute to diverse skeletal outcomes. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene networks and have appeared as indicators of toxicant-induced perturbation. In this study, we examined whether developmentally relevant toxicants are associated with miRNA regulatory networks during osteogenic differentiation. Using a human embryonic stem cell (hESC)-based osteogenic differentiation model, we assessed the effects of nine toxicants spanning distinct primary mechanisms. Toxicant exposure impaired osteogenic differentiation at their IC50, as reflected by altered expression of osteogenic markers and transcriptional remodeling. Global miRNA profiling revealed dysregulation of miRNAs enriched for bone-related biological processes, including regulators of osteogenic commitment and differentiation timing. Integrated miRNA–mRNA network analysis identified a subset of miRNAs linked to core osteogenic and lineage-associated pathways, including RUNX2-dependent transcription and BMP and Wnt signaling. Modulation of representative miRNAs produced osteogenic outcomes consistent with those observed following toxicant exposure and, in some cases, was associated with partial restoration of differentiation in exposed cultures. Collectively, these findings indicate that chemically diverse developmental toxicants are associated with miRNA-mediated regulatory patterns during osteogenic differentiation. Identification of conserved miRNA signatures provides mechanistic insight into developmental bone toxicity and supports the use of miRNA network analysis as a human-relevant endpoint for skeletal hazard identification.
2026-05-31 | GSE324490 | GEO
Project description:Tissue resident macrophages (MTRs) regulate tissue repair and homeostasis by clearing cell debris, and are thought to form the first line of defense against pathogens. MTRs form early in life and self-renew locally. However, during tissue damage or disease, bone-marrow derived monocytes enter tissue sites and differentiate into MTRs, repairing the tissue and replenishing macrophages in the niche. How MTR versus monocyte-derived macrophages recruited during inflammation contribute to health and disease, and the cell-intrinsic mechanisms that control the monocyte to MTR transition across tissues, remain elusive. Here we show that deoxyhypusine synthase (DHPS), an enzyme that mediates the spermidine-dependent hypusine modification of the translation factor eIF5A, is required for the differentiation and maintenance of MTR. EIF5A is the only protein to contain hypusine, and the only function of DHPS (together with DOHH) is to hypusinate eIF5A. Hypusinated-eIF5A enhances the translation efficiency of certain mRNA transcripts that lead to ribosome stalling, including those with polyproline motifs. MTRs in tissues of young mice with myelomonocytic cell deletions in DHPS (Dhps-M mice; hypusination deficient eIF5A) had abnormal expression of macrophage tissue resident markers, and MTRs themselves declined with age. Single cell transcriptional analysis of DHPS-deficient peritoneal macrophages indicated a block in the transition from monocyte to mature MTRs, while proteomics revealed decreased expression of cell adhesion and signaling molecules. Notably, sequencing of ribosome-engaged transcripts suggested that certain cell adhesion and signaling molecules are hyper-dependent on hypusinated eIF5A for efficient translation.
2026-03-23 | PXD054670 | Pride
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.
2018-10-26 | PXD011238 | Pride
Project description:Ischemic stroke promotes monocyte recruitment to the injured brain and their differentiation into monocyte-derived macrophages (MDMs). These cells contribute to debris clearance but may also exacerbate neuroinflammation. However, the heterogeneity of macrophage subsets and the phenotypic transitions that shape MDM functional states during the subacute phase of stroke remain incompletely characterized. To address this, we first performed single-cell RNA sequencing (scRNA-seq) to define the transcriptional landscape of the mouse brain 48 hours after transient middle cerebral artery occlusion/reperfusion compared with sham controls. Reclustering of macrophage-lineage cells identified multiple monocyte-derived subsets, including a distinct Cd68hi/Ctsdhi MDM subset enriched for lysosomal and lipid-processing gene expression programs. Cell trajectory inference supported a transition from inflammatory infiltrates toward the Cd68hi/Ctsdhi state, accompanied by induction of transcriptomic networks that drive macrophage function to favor a clearance-competent phenotype in response to ischemic stroke. Complementary single-cell ATAC sequencing (scATAC-seq) demonstrated cell type-specific chromatin remodeling after stroke and revealed MDM subclusters with accessibility at key loci regulating lysosomal function and lipid metabolism. Together, our findings define a cellular and regulatory framework of the subacute post-stroke brain and identify a lysosome-enriched Cd68hi/Ctsdhi MDM trajectory, highlighting endolysosomal and lipid-processing programs during early stroke recovery.
2026-05-15 | GSE326241 | GEO
Project description:Ischemic stroke promotes monocyte recruitment to the injured brain and their differentiation into monocyte-derived macrophages (MDMs). These cells contribute to debris clearance but may also exacerbate neuroinflammation. However, the heterogeneity of macrophage subsets and the phenotypic transitions that shape MDM functional states during the subacute phase of stroke remain incompletely characterized. To address this, we first performed single-cell RNA sequencing (scRNA-seq) to define the transcriptional landscape of the mouse brain 48 hours after transient middle cerebral artery occlusion/reperfusion compared with sham controls. Reclustering of macrophage-lineage cells identified multiple monocyte-derived subsets, including a distinct Cd68hi/Ctsdhi MDM subset enriched for lysosomal and lipid-processing gene expression programs. Cell trajectory inference supported a transition from inflammatory infiltrates toward the Cd68hi/Ctsdhi state, accompanied by induction of transcriptomic networks that drive macrophage function to favor a clearance-competent phenotype in response to ischemic stroke. Complementary single-cell ATAC sequencing (scATAC-seq) demonstrated cell type-specific chromatin remodeling after stroke and revealed MDM subclusters with accessibility at key loci regulating lysosomal function and lipid metabolism. Together, our findings define a cellular and regulatory framework of the subacute post-stroke brain and identify a lysosome-enriched Cd68hi/Ctsdhi MDM trajectory, highlighting endolysosomal and lipid-processing programs during early stroke recovery.
2026-05-15 | GSE326118 | GEO
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.
2020-05-26 | PXD009514 | Pride