Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206977 | GEO | 2022/10/06
REPOSITORIES: GEO
Similar Datasets
Project description:Heterogeneity of endothelial cell (EC) populations reflects their diverse functions in maintaining tissue's homeostasis. However, their phenotypic, molecular, and functional properties are not entirely mapped. We use the Tie2-CreERT2;Rosa26-tdTomato reporter mouse to trace, profile, and cultivate primary ECs from different organs. As paradigm platform, we use this strategy to study bone marrow endothelial cells (BMECs). Single-cell mRNA sequencing of primary BMECs reveals that their diversity and native molecular signatures is transitorily preserved in an ex vivo culture that conserves key cell-to-cell microenvironment interactions. Macrophages sustain BMEC cellular diversity and expansion and preserve sinusoidal-like BMECs ex vivo. Endomucin expression discriminates BMECs in populations exhibiting mutually exclusive properties and distinct sinusoidal/arterial and tip/stalk signatures. In contrast to arterial-like, sinusoidal-like BMECs are short-lived, form 2D-networks, contribute to in vivo angiogenesis, and support hematopoietic stem/progenitor cells in vitro. This platform can be extended to other organs' ECs to decode mechanistic information and explore therapeutics.
| S-EPMC9700769 | biostudies-literature
Project description:Heterogeneity of endothelial cell populations reflects their diverse functions in maintaining tissue’s homeostasis. However, their phenotypic, molecular, and functional properties are not entirely mapped. We used a new Tie2-CreERT2;Rosa26-tdTomato reporter mouse to trace, profile, and cultivated primary ECs from different organs. As platform paradigm, we used this strategy to study bone marrow endothelial cells (BMEC). Single-cell mRNA sequencing of primary BMEC revealed that their diversity and native molecular signatures is transitorily preserved in an ex-vivo culture that conserves key cell-to-cell microenvironment interactions. Macrophages sustained primary BMEC cellular diversity and expansion and were critical to preserve sinusoidal-like BMEC ex-vivo. Expression of endomucin discriminated BMEC in populations exhibiting mutually exclusive properties and distinct tip and stalk signatures. In contrast to arterial-like, sinusoidal-like BMECs were short-lived, formed 2D-networks, contributed to in-vivo angiogenesis and supported hematopoietic stem/progenitor cells in-vitro. This platform can be extended to other organs’ ECs to decode mechanistic information and explore therapeutics.
2022-10-07 | GSE206976 | GEO
Project description:Heterogeneity of endothelial cell populations reflects their diverse functions in maintaining tissue’s homeostasis. However, their phenotypic, molecular, and functional properties are not entirely mapped. We used a new Tie2-CreERT2;Rosa26-tdTomato reporter mouse to trace, profile, and cultivated primary ECs from different organs. As platform paradigm, we used this strategy to study bone marrow endothelial cells (BMEC). Single-cell mRNA sequencing of primary BMEC revealed that their diversity and native molecular signatures is transitorily preserved in an ex-vivo culture that conserves key cell-to-cell microenvironment interactions. Macrophages sustained primary BMEC cellular diversity and expansion and were critical to preserve sinusoidal-like BMEC ex-vivo. Expression of endomucin discriminated BMEC in populations exhibiting mutually exclusive properties and distinct tip and stalk signatures. In contrast to arterial-like, sinusoidal-like BMECs were short-lived, formed 2D-networks, contributed to in-vivo angiogenesis and supported hematopoietic stem/progenitor cells in-vitro. This platform can be extended to other organs’ ECs to decode mechanistic information and explore therapeutics.
2022-10-07 | GSE206975 | GEO
Project description:Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelial cells
| PRJNA853186 | ENA
Project description:Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelial cells [scRNA-Seq]
| PRJNA853189 | ENA
Project description:Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelial cells [bulk RNA-seq]
| PRJNA853187 | ENA
Project description:BackgroundGenes are created by a variety of evolutionary processes, some of which generate duplicate copies of an entire gene, while others rearrange pre-existing genetic elements or co-opt previously non-coding sequence to create genes with 'novel' sequences. These novel genes are thought to contribute to distinct phenotypes that distinguish organisms. The creation, evolution, and function of duplicated genes are well-studied; however, the genesis and early evolution of novel genes are not well-characterized. We developed a computational approach to investigate these issues by integrating genome-wide comparative phylogenetic analysis with functional and interaction data derived from small-scale and high-throughput experiments.ResultsWe examine the function and evolution of new genes in the yeast Saccharomyces cerevisiae. We observed significant differences in the functional attributes and interactions of genes created at different times and by different mechanisms. Novel genes are initially less integrated into cellular networks than duplicate genes, but they appear to gain functions and interactions more quickly than duplicates. Recently created duplicated genes show evidence of adapting existing functions to environmental changes, while young novel genes do not exhibit enrichment for any particular functions. Finally, we found a significant preference for genes to interact with other genes of similar age and origin.ConclusionsOur results suggest a strong relationship between how and when genes are created and the roles they play in the cell. Overall, genes tend to become more integrated into the functional networks of the cell with time, but the dynamics of this process differ significantly between duplicate and novel genes.
| S-EPMC3046487 | biostudies-literature
Project description:Bone marrow endothelial cells (BMECs) play a key role in bone formation and haematopoiesis. Although recent studies uncovered the cellular taxonomy of stromal compartments in the bone marrow (BM), the complexity of BMECs is not fully characterized. In the present study, using single-cell RNA sequencing, we defined a spatial heterogeneity of BMECs and identified a capillary subtype, termed type S (secondary ossification) endothelial cells (ECs), exclusively existing in the epiphysis. Type S ECs possessed unique phenotypic characteristics in terms of structure, plasticity and gene expression profiles. Genetic experiments showed that type S ECs atypically contributed to the acquisition of bone strength by secreting type I collagen, the most abundant bone matrix component. Moreover, these cells formed a distinct reservoir for haematopoietic stem cells. These findings provide the landscape for the cellular architecture in the BM vasculature and underscore the importance of epiphyseal ECs during bone and haematopoietic development.
| S-EPMC10567563 | biostudies-literature
Project description:IntroductionPoor graft function (PGF), characterized by myelosuppression, represents a significant challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human cytomegalovirus (HCMV) being established as a risk factor for PGF. However, the underlying mechanism remains unclear. Bone marrow endothelial progenitor cells (BM-EPCs) play an important role in supporting hematopoiesis and their dysfunction contributes to PGF development. We aim to explore the effects of CMV on BM-EPCs and its underlying mechanism.MethodsWe investigated the compromised functionality of EPCs derived from individuals diagnosed with HCMV viremia accompanied by PGF, as well as after infected by HCMV AD 169 strain in vitro, characterized by decreased cell proliferation, tube formation, migration and hematopoietic support, and increased apoptosis and secretion of TGF-β1.ResultsWe demonstrated that HCMV-induced TGF-β1 secretion by BM-EPCs played a dominant role in hematopoiesis suppression in vitro experiment. Moreover, HCMV down-regulates Vitamin D receptor (VDR) and subsequently activates p38 MAPK pathway to promote TGF-β1 secretion by BM-EPCs.DiscussionHCMV could infect BM-EPCs and lead to their dysfunction. The secretion of TGF-β1 by BM-EPCs is enhanced by CMV through the activation of p38 MAPK via a VDR-dependent mechanism, ultimately leading to compromised support for hematopoietic progenitors by BM EPCs, which May significantly contribute to the pathogenesis of PGF following allo-HSCT and provide innovative therapeutic strategies targeting PGF.
| S-EPMC11445044 | biostudies-literature
Project description:BackgroundImmune-related hemocytopenia (IRH) is a type of autoimmune disease that targets bone marrow hematopoietic cells. This study investigated the influence of atorvastatin on the functional aspects of bone marrow endothelial progenitor cells (BM EPCs) in IRH patients.MethodsBM EPCs were isolated from 15 patients with IRH and 20 normal controls. The isolated BM EPCs were characterized by flow cytometry. Cell counting kit-8, flow cytometry, and Transwell migration assays were used to determine the proliferation, apoptosis, and migration of BM EPCs, respectively. Protein levels were determined by western blot assay.ResultsThe BM EPCs isolated from IRH patients showed reduced proliferation, increased apoptosis, and attenuated migratory ability compared to those from normal controls. Western blot analysis showed that the protein level of p-p38 was significantly increased, while that of Phosphorylated protein kinase B (p-AKT) was significantly decreased in the BM EPCs from IRH patients, compared to BM EPCs from healthy subjects. Cell proliferation and migration were significantly enhanced by atorvastatin, recombinant human thrombopoietin, and SB20358 compared to the untreated BM EPCs from IRH patients. Atorvastatin, Recombinant human thrombopoietin (TPO), and SB20358 treatment significantly suppressed the protein levels of p-p38 protein, but increased those of p-AKT in BM EPCS from IRH patients.ConclusionsIn summary, atorvastatin increases the number and function of BM EPCs in IRH patients by regulating the p38 and AKT signaling pathways.
| S-EPMC8350688 | biostudies-literature