Similar Datasets
Project description:The incidence of cutaneous T-cell lymphoma (CTCL) increases with age, and blood involvement portends a worse prognosis. To advance our understanding of the development of CTCL and identify potential therapeutic targets, we performed integrative analyses of paired single-cell RNA and T-cell receptor (TCR) sequencing of peripheral blood CD4+ T cells from patients with CTCL to reveal disease-unifying features. The malignant CD4+ T cells of CTCL showed highly diverse transcriptomic profiles across patients, with most displaying a mature Th2 differentiation and T-cell exhaustion phenotype. TCR-CDR3 peptide prediction analysis suggested limited diversity between CTCL samples, consistent with a role for a common antigenic stimulus. Potential of heat diffusion for affinity-based trajectory embedding transition analysis identified putative precancerous circulating populations characterized by an intermediate stage of gene expression and mutation level between the normal CD4+ T cells and malignant CTCL cells. We further revealed the therapeutic potential of targeting CD82 and JAK that endow the malignant CTCL cells with survival and proliferation advantages.
| S-EPMC9979716 | biostudies-literature
Project description:Integrated transcriptome and trajectory analysis of cutaneous T-cell identifies putative precancer cell populations
| PRJNA811209 | ENA
Project description:Despite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly characterized, as does the precise molecular mechanisms underlying the balance between self-renewal and differentiation. Here we carried out a systematic meta-analysis of published gene expression data to rank-order genes based on their likelihood of regulating ESC identity. Not only did our analysis correctly rank known pluripotency-associated genes atop the list, but it also helped unearth many novel determinants of ESC identity including several components of functionally distinct complexes, as determined using RNAi. We focus on our top-hit Nucleolin, and characterize its mechanistic role in the maintenance of ESC homeostasis by shielding from differentiation-inducing redox imbalance-induced oxidative stress. Notably, we identify a conceptually novel mechanism involving a Nucleolin-dependent bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our gene ranks represent a rich and valuable resource for uncovering novel ESC regulators. Microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Ncl siRNA #1 (Invitrogen, 17975-MSS206961) Ncl siRNA #2 (Invitrogen, 17975-MSS275939), and Control siRNA duplex targeting firefly luciferase.
2014-03-26 | E-GEOD-47872 | biostudies-arrayexpress
Project description:Detailed transcriptomic analyses of differentiated cell populations derived from human pluripotent stem cells is routinely used to assess the identity and utility of the differentiated cells. In particular, single cell RNA-sequencing (scRNA-seq) can provide insights into both the cellular and transcriptional heterogeneity of differentiated cell populations. Here we provide scRNA-seq data obtained from ROR1-expressing lens epithelial cells (ROR1e LECs) obtained via directed differentiation of CA1 human embryonic stem cells. Through the use of principal component analysis, heat maps and gene ontology assessments, we demonstrate that ROR1e LECs represent a highly purified and large-scale population of lens cells. These data provide a resource for future characterisation of both normal and cataractous human lens biology.
2020-11-27 | E-MTAB-9178 | biostudies-arrayexpress
Project description:CTCLs are a group of non-Hodgkin lymphomas, with non-aggressive forms (Mycosis fungoides (MF)) initially presenting with features of cutaneous eczema or psoriasis, posing a challenge for clinical and histological diagnosis. Using scRNA-seq, we hope to delineate the molecular signatures of CTCL to provide novel avenues for diagnostics and therapies.
2024-11-11 | E-MTAB-12303 | biostudies-arrayexpress
Project description:During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone marrow-derived hematopoietic progenitors that migrate through the bloodstream. The current understanding of the nature of thymic immigrants is largely based on data from pre-clinical models. Here, we employed single-cell RNA sequencing (scRNA-seq) to examine the immature postnatal thymocyte population in humans. Integration of bone marrow and peripheral blood precursor datasets identified two putative thymus seeding precursors that varied in expression of CD7; CD10; and the homing receptors CCR7, CCR9, and ITGB7. Whereas both precursors supported T cell development, only one contributed to intrathymic dendritic cell (DC) differentiation, predominantly of plasmacytoid dendritic cells. Trajectory inference delineated the transcriptional dynamics underlying early human T lineage development, enabling prediction of transcription factor (TF) modules that drive stage-specific steps of human T cell development. This comprehensive dataset defines the expression signature of immature human thymocytes and provides a resource for the further study of human thymopoiesis.
2020-04-17 | GSE144870 | GEO
Project description:Time-series single-cell RNA sequencing (scRNA-seq) data in biology has opened the door to elucidate cell differentiation processes. In this context, the optimal transport theory has attracted attention to interpolate scRNA-seq data in adjacent times and infer the trajec- tories of cell differentiation. This paper presents scEGOT, a novel comprehensive single-cell trajectory inference framework based on entropic Gaussian mixture optimal transport (EGOT). The method- ology facilitates the inference of cell differentiation pathways and dynamics from time-series scRNA-seq data. The scEGOT frame- work provides comprehensive outputs, including cell state graphs, velocity fields of cell differentiation, time interpolations of scRNA- seq data, space-time continuous videos of cell differentiation with gene expressions, gene regulatory networks, and reconstructions of Waddington’s epigenetic landscape. These outputs allow us to un- derstand the dynamics of the cell differentiation process from mul- tiple perspectives. To demonstrate that scEGOT is a powerful and versatile tool for single-cell biology, it was applied to time-series scRNA-seq data of the human primordial germ cell-like cell (human PGCLC) induction system. This application provided new insights into the mechanism of PGCLC/somatic cell segregation. In particu- lar, we identified the PGCLC progenitor population and the time point of the segregation. In addition, we found novel key genes that may be critical for human PGCLC differentiation.
2024-11-08 | GSE241287 | GEO
Project description:A limitation in the application of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) is the failure of these cells to achieve full functional maturity. The mechanisms by which directed differentiation differs from endogenous development, leading to consequent PSC-CM maturation arrest, remain unclear. Here, we generate a single-cell RNA sequencing (scRNA-seq) reference of mouse in vivo CM maturation with extensive sampling of previously difficult-to-isolate perinatal time periods. We subsequently generate isogenic embryonic stem cells to create an in vitro scRNA-seq reference of PSC-CM-directed differentiation. Through trajectory reconstruction, we identify an endogenous perinatal maturation program that is poorly recapitulated in vitro. By comparison with published human datasets, we identify a network of nine transcription factors (TFs) whose targets are consistently dysregulated in PSC-CMs across species. Notably, these TFs are only partially activated in common ex vivo approaches to engineer PSC-CM maturation. Our study can be leveraged toward improving the clinical viability of PSC-CMs.
| S-EPMC10545814 | biostudies-literature
Project description:Despite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly characterized, as does the precise molecular mechanisms underlying the balance between self-renewal and differentiation. Here we carried out a systematic meta-analysis of published gene expression data to rank-order genes based on their likelihood of regulating ESC identity. Not only did our analysis correctly rank known pluripotency-associated genes atop the list, but it also helped unearth many novel determinants of ESC identity including several components of functionally distinct complexes, as determined using RNAi. We focus on our top-hit Nucleolin, and characterize its mechanistic role in the maintenance of ESC homeostasis by shielding from differentiation-inducing redox imbalance-induced oxidative stress. Notably, we identify a conceptually novel mechanism involving a Nucleolin-dependent bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our gene ranks represent a rich and valuable resource for uncovering novel ESC regulators.
2014-03-26 | GSE47872 | GEO
Project description:Background and objectiveAtrial fibrillation (AF) and coronary heart disease (CHD) are closely related to metabolic dysregulation. However, the metabolic characteristics of AF patients with concomitant CHD remain unclear. The aims of this study were to elucidate the metabolic profiles of patients with AF and CHD to seek new therapeutic targets and related factors of AF combined with CHD.MethodsUntargeted metabolomics and targeted oxylipins profiling were performed to characterize the serum metabolome landscape of patients with AF, CHD, and AF comorbid CHD.ResultsThe serum metabolic fingerprints of patients with AF comorbid CHD were significantly differentiated from normal controls (NC) and individuals with AF or CHD alone, and the differentiated metabolites dominated by a variety of lipid alterations in the phospholipid and fatty acid metabolism. Furthermore, the targeted profiles of oxylipins demonstrated that the levels of arachidonic acid derivatives including prostaglandins, leukotrienes, hydroxy-docosahexaenoic acids, hydroxy-eicostetraenoic acids and hydroxy-eicosatrienoic acids in patients with AF and CHD were significantly different from those in the NC, AF, and CHD groups. Several prostaglandins were positively associated with echocardiographic indicators of myocardial remodeling.ConclusionsThis study updates metabolic insights of AF and CHD and provides potential therapeutic targets for preventing or treating AF comorbid CHD.
| S-EPMC11538890 | biostudies-literature