Recapitulate Organotypic Mesenchyme and Endothelium via Vascularized Lung and Intestine Organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1053817 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Organotypic mesenchyme and endothelium are pivotal during organ development. To generate these context-specific cell types, we established human pluripotent stem cell (hPSC)-derived meso-endoderm spheroids and vascularized primitive gut tube organoids and benchmarked this process via single-cell RNA-seq.
2025-06-29 | GSE250399 | GEO
Project description:Mouse Vascularized Adipose Spheroids: An Organotypic Model for Thermogenic Adipocytes
| PRJNA1086355 | ENA
Project description:Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues’ thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by factors like cold exposure, share mechanisms that drive non-shivering thermogenesis. Understanding their behavior requires sophisticated, yet universal in vitro models that replicate the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue. We show that scaffold embedding improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to 2D cultures, which was further enhanced by β-adrenergic receptor stimulation via isoproterenol correlating with elevated β-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, our vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes.
2024-05-02 | GSE261267 | GEO
Project description:High throughput quantitative whole transcriptome analysis of E18.5 mouse distal lung mesenchyme and endothelium
| PRJNA807654 | ENA
Project description:To identify proteins phosphorylated by Akt downstream of PI3K-mediated PDGFRalpha signaling, we immunoprecipitated Akt phosphorylation substrates from PDGF-AA-treated primary mouse embryonic palatal mesenchyme (MEPM) lysates and analyzed the peptides by nano LC-MS/MS.
2019-06-04 | PXD000779 | Pride
Project description:Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs). The MSCs initiated condensation within these heterotypic cell mixtures, which was dependent upon substrate matrix stiffness. Defining optimal mechanical properties promoted formation of 3D, transplantable organ buds from tissues including kidney, pancreas, intestine, heart, lung, and brain. Transplanted pancreatic and renal buds were rapidly vascularized and self-organized into functional, tissue-specific structures. These findings provide a general platform for harnessing mechanical properties to generate vascularized, complex organ buds with broad applications for regenerative medicine. Gene expression profiles of development-related gene expression in kidney bud transplants and murine kidneys.
2015-07-01 | E-GEOD-66454 | biostudies-arrayexpress
Project description:To investigate the cell-cell interactions among the transplanted vascularized organoids, we utilized a Slide-seq-based spatial transcriptomics platform to unbiasedly map the spatial distribution of ligand-receptor pairs.
2025-06-29 | GSE296429 | GEO
Project description:Background: Triple-negative breast cancer (TNBC) is characterized by its highly aggressive pathology and limited number of approved targeted therapies. Emerging evidence suggests that stromal cells within the tumor microenvironment (TME) play a crucial role in TNBC progression, making them potential therapeutic targets. Yet the molecular basis of stromal cell activation and tumor-stromal crosstalk in TNBC is poorly understood, limiting the development of therapies targeted to this axis. Methods: To explore potential therapeutic targets within the stromal niche of TNBC, we employed an advanced human in vitro microphysiological system model – the vascularized microtumor (VMT) – in which perfused vascular networks within a microfluidic platform self-assemble in a complex extracellular matrix (ECM) and supply nutrients and drugs to growing tumors. By leveraging single-cell RNA sequencing (scRNA-seq), we investigated gene expression patterns, cellular heterogeneity, and intercellular communication within TNBCs. Results: Our analysis revealed that histopathologically-normal human breast tissue-derived stromal cells activate neoplastic signaling pathways when exposed to the TNBC TME. Through a comparison of these interactions in VMTs with scRNA-seq data obtained from clinical specimens, we successfully identified therapeutic targets situated at the tumor-stromal interface that hold potential clinical significance. Promising results were observed in TNBC VMTs when combining treatments that target Tie2 signaling, thereby normalizing vasculature, with tumor-targeted paclitaxel. Furthermore, dual inhibition of Her3 and Akt also demonstrated efficacy against TNBC. Conclusions: By using an organotypic in vitro VMT model to recapitulate key components of the TNBC TME, we demonstrate the potential of inducing a favorable tumor microenvironment as a targeted therapeutic approach in TNBC.
2024-01-05 | GSE238090 | GEO
Project description:Replacement of lost beta cells in patients with diabetes has the potential to alleviate them of their disease, yet current protocols to make beta cells are inadequate for therapy. In vitro screens can reveal the signals necessary for endocrine maturation to improve beta cell production, however the complexities of in vivo development that lead to beta cell formation are lost in two-dimensional systems. Here, we create three-dimensional organotypic pancreatic cultures, named pancreatoids, composed of embryonic day 10.5 murine epithelial progenitors and native mesenchyme. These progenitors assemble in scaffold-free, floating conditions and, with the inclusion of native mesenchyme, develop into pancreatoids expressing markers of different pancreatic lineages including endocrine-like cells. Treatment of pancreatoids with (-)-Indolactam-V or phorbol 12-myristate 13-acetate, two protein kinase C activators, leads to altered morphology which otherwise would be overlooked in two-dimensional systems. Protein kinase C activation also led to fewer Insulin+ cells, decreased Ins1 and Ins2 mRNA levels, and increased Pdx1 and Hes1 mRNA levels with a high number of DBA+ cells. Thus, organotypic pancreatoids provide a useful tool for developmental studies, and can further be used for disease modeling, small molecules and genetic screens, or applied to human pluripotent stem cell differentiation for beta-like cell formation.
| S-EPMC5589819 | biostudies-literature
Project description:The poor osseointegration of dental implants in diabetic patients has become a long-standing clinical problem. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes vascularized osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants sucessfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data proved that Mg2+ promoted vascularized osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
2024-02-07 | GSE236139 | GEO