Single cell transcriptomics reveals new insights on the dynamical function of transcription factors during blood stem and progenitor cell formation
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA380270PRJNA380304PRJNA379852PRJNA380221PRJNA379854
ORGANISM(S): other sequences Mus musculus Homo sapiens
PROVIDER: GSE96986 | GEO | 2018/03/20
REPOSITORIES: GEO
Similar Datasets
Project description:Single cell transcriptomics reveals new insights on the dynamical function of transcription factors during blood stem and progenitor cell formation
| PRJNA380270 | ENA
Project description:Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers. Within the heptad, we identified two sets of factors of opposing functions: one (Erg/Fli1) promoting the endothelial cell fate, the other (Runx1/Gata2) promoting the hematopoietic fate. Surprisingly, our data suggest that even though Fli1 initially supports the endothelial cell fate, it acquires a pro-hematopoietic role when co-expressed with Runx1. This work demonstrates the power of single-cell RNA-sequencing for characterizing complex transcription factor dynamics.
| S-EPMC5860872 | biostudies-literature
Project description:AimsFluid shear stress (SS) is known to regulate endothelial cell (EC) function. Most of the studies, however, focused on the effects of cell-free fluid-generated wall SS on ECs. The objective of this study was to investigate how changes in blood flow altered EC signalling and endothelial function directly through wall SS and indirectly through SS effects on red blood cells (RBCs).Methods and resultsExperiments were conducted in individually perfused rat venules. We experimentally induced changes in SS that were quantified by measured flow velocity and fluid viscosity. The concomitant changes in EC [Ca2+]i and nitric oxide (NO) were measured with fluorescent markers, and EC barrier function was assessed by fluorescent microsphere accumulation at EC junctions using confocal imaging. EC eNOS activation was evaluated by immunostaining. In response to changes in SS, increases in EC [Ca2+]i and gap formation occurred only in blood or RBC solution perfused vessels, whereas SS-dependent NO production and eNOS-Ser1177 phosphorylation occurred in both plasma and blood perfused vessels. A bioluminescent assay detected SS-dependent ATP release from RBCs. Pharmacological inhibition and genetic modification of pannexin-1 channels on RBCs abolished SS-dependent ATP release and SS-induced increases in EC [Ca2+]i and gap formation.ConclusionsSS-induced EC NO production occurs in both cell free fluid and blood perfused vessels, whereas SS-induced increases in EC [Ca2+]i and EC gap formation require the presence of RBCs, attributing to SS-induced pannexin-1 channel dependent release of ATP from RBCs. Thus, changes in blood flow alter vascular EC function through both wall SS and SS exerted on RBCs, and RBC released ATP contributes to SS-induced changes in EC barrier function.
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Project description:Research has shown that, apart from androgen-sensitive dermal papilla cells, hair follicle progenitor cell dynamics play a critical role in androgenetic alopecia (AGA). This study focuses on these progenitor cells, applying the spatial transcriptome technique to reveal molecular disturbances in the progenitor cells (CD34+ area) between AGA patients (PG-A) and normal controls (PG-C).
2024-11-27 | GSE282856 | GEO
Project description:BackgroundThe contributions of various types of cell populations in dialysis-related peritoneal fibrosis are poorly understood. Single-cell RNA sequencing brings single-cell level resolution to the analysis of cellular transcriptomics, which provides a new way to further characterize the distinct roles and functional states of each cell population during peritoneal fibrosis.MethodsSingle-cell transcriptomics from normal peritoneal tissues of six patients, from effluent of patients with short-term peritoneal dialysis (less than 2 weeks, n = 6), and from long-term peritoneal dialysis patients (more than 6 years, n = 4) were analyzed.ResultsWe identified a distinct cell component between samples among different groups. Functional analysis of the differentially expressed genes identified cell type specific biological processes relevant to different fibrosis stages. Well-known key molecular mechanisms participating in the pathophysiology of peritoneal fibrosis were vitrified, and some of them were found to be restricted to specific cell types. Gradually growing enrichment of PI3K/AKT/mTOR pathway and impairment of oxidative phosphorylation in mesothelial cells and fibroblasts were found from healthy control, short-term dialysis, to long-term dialysis, respectively. The fibroblasts' population obtained from the patients, who received peritoneal dialysis, showed a functional characteristic of immune-chemotaxis and immune response, which was characterized by broadly significant increase in the expression of interleukins, chemokines, cytokines, and human leukocyte antigens. Furthermore, we described the intercellular crosstalk networks based on receptor-ligand interactions, and highlighted a central role of fibroblasts in regulating the key mechanisms of peritoneal fibrosis through crosstalk with other cells.ConclusionsIn summary, despite describing information for fibrogenic molecular mechanisms in the resolution level of individual cell populations, this work identifies the significant functional evolution of fibroblasts during peritoneal fibrosis. This study also reveals the intercellular receptor-ligand interactions in which the fibroblasts serve as a major node, eventually providing new insights into the role of fibroblasts during disease pathogenesis.
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Project description:Drosophila blood cells called hemocytes form an efficient barrier against infections and tissue damage. During metamorphosis, hemocytes undergo tremendous changes in their shape and behavior, preparing them for tissue clearance. Yet, the diversity and functional plasticity of pupal blood cells have not been explored. Here, we combine single-cell transcriptomics and high-resolution microscopy to dissect the heterogeneity and plasticity of pupal hemocytes. We identified undifferentiated and specified hemocytes with different molecular signatures associated with distinct functions such as antimicrobial, antifungal immune defense, cell adhesion or secretion. Strikingly, we identified a highly migratory and immune-responsive pupal cell population expressing typical markers of the posterior signaling center (PSC), which is known to be an important niche in the larval lymph gland. PSC-like cells become restricted to the abdominal segments and are morphologically very distinct from typical Hemolectin (Hml)-positive plasmatocytes. G-TRACE lineage experiments further suggest that PSC-like cells can transdifferentiate to lamellocytes triggered by parasitoid wasp infestation. In summary, we present the first molecular description of pupal Drosophila blood cells, providing insights into blood cell functional diversification and plasticity during pupal metamorphosis.
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Project description:The blood-brain barrier (BBB) is a highly complex and dynamic barrier. It is formed by an interdependent network of brain capillary endothelial cells, endowed with barrier properties, and perivascular cells (astrocytes and pericytes) responsible for inducing and maintaining those properties. One of the primary properties of the BBB is a strict regulation of paracellular permeability due to the presence of junctional complexes (tight, adherens and gap junctions) between the endothelial cells. Alterations in junction assembly and function significantly affect BBB properties, particularly barrier permeability. However, such alterations are also involved in remodeling the brain endothelial cell surface and regulating brain endothelial cell phenotype. This review summarizes the characteristics of brain endothelial tight, adherens and gap junctions and highlights structural and functional alterations in junctional proteins that may contribute to BBB dysfunction.
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Project description:The dynamical structure factor is one of the experimental quantities crucial in scrutinizing the validity of the microscopic description of strongly correlated systems. However, despite its long-standing importance, it is exceedingly difficult in generic cases to numerically calculate it, ensuring that the necessary approximations involved yield a correct result. Acknowledging this practical difficulty, we discuss in what way results on the hardness of classically tracking time evolution under local Hamiltonians are precisely inherited by dynamical structure factors and, hence, offer in the same way the potential computational capabilities that dynamical quantum simulators do: We argue that practically accessible variants of the dynamical structure factors are bounded-error quantum polynomial time ([Formula: see text])-hard for general local Hamiltonians. Complementing these conceptual insights, we improve upon a novel, readily available measurement setup allowing for the determination of the dynamical structure factor in different architectures, including arrays of ultra-cold atoms, trapped ions, Rydberg atoms, and superconducting qubits. Our results suggest that quantum simulations employing near-term noisy intermediate-scale quantum devices should allow for the observation of features of dynamical structure factors of correlated quantum matter in the presence of experimental imperfections, for larger system sizes than what is achievable by classical simulation.
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Project description:The aim of this study was to evaluate the effect of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, on red blood cell parameters in the context of iron homeostasis in patients with tuberous sclerosis complex (TSC) and evaluate its effect on cell size in vitro. Everolimus has a significant impact on red blood cell parameters in patients with TSC. The most common alteration was microcytosis. The mean MCV value decreased by 9.2%, 12%, and 11.8% after 3, 6, and 12 months of everolimus treatment. The iron level declined during the first 3 months, and human soluble transferrin receptor concentration increased during 6 months of therapy. The size of K562 cells decreased when cultured in the presence of 5 μM everolimus by approximately 8%. The addition of hemin to the cell culture with 5 μM everolimus did not prevent any decrease in cell size. The stage of erythroid maturation did not affect the response to everolimus. Our results showed that the mTOR inhibitor everolimus caused red blood cell microcytosis in vivo and in vitro. This effect is not clearly related to a deficit of iron and erythroid maturation. This observation confirms that mTOR signaling plays a complex role in the control of cell size.
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