Ontology highlight
ABSTRACT:
PROVIDER: PRJNA736575 | ENA |
REPOSITORIES: ENA
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Project description:Self-organizing in vitro mouse neural tube organoids mimic embryonic development
| PRJNA888056 | ENA
Project description:Harnessing the self-organizing abilities of human embryonic stem cells to mimic normal and aberrant development is a pressing challenge. Generation of highly reproducible and standardized models would allow drug screening with unprecedented accuracy. Here we report single-cell RNA-seq data (10xGenomics) of human "neuruloids". Using micro-patterned technologies we recapitulate the self-organization of the complete human embryonic ectodermal compartment during neurulation containing: neural progenitors, neural crest, sensory placode and epidermis. Single-cell transcriptomics allowed the precise molecular characterization of each cell type in a faithful model of human neurulation. Additionally, isogenic neuruloids coupled to deep neural network analysis provide a unique opportunity to model human neuropathological disorders as demonstrated for Huntignton’s disease.
2019-09-08 | GSE118682 | GEO
Project description:Knowledge of cell signaling pathways that drive human neural crest differentiation into craniofacial chondrocytes is incomplete, yet essential for using stem cells to regenerate craniomaxillofacial structures. To accelerate translational progress, we developed a differentiation protocol that generated self-organizing craniofacial cartilage organoids from human embryonic stem cell-derived neural crest stem cells. Histological staining of cartilage organoids revealed tissue architecture and staining typical of elastic cartilage. Protein and post-translational modification (PTM) mass spectrometry and snRNASeq data showed that chondrocyte organoids expressed robust levels of cartilage extracellular matrix (ECM) components: many collagens, aggrecan, perlecan, proteoglycans, and elastic fibers. We identified two populations of chondroprogenitor cells, mesenchyme cells and nascent chondrocytes and the growth factors involved in paracrine signaling between them. We show that ECM components secreted by chondrocytes not only create a structurally resilient matrix that defines cartilage, but also play a pivotal autocrine cell signaling role to determine chondrocyte fate.
2024-04-04 | PXD050668 | Pride
Project description:The capacity of 3D organoids to mimic physiological tissue organization and functionality has provided an invaluable tool to model development and disease in vitro. However, conventional organoid cultures primarily represent the homeostasis of self-organizing including VPA, EPZ6438, LDN193189, and R-Spondin 1 conditioned medium, which mimics the gut epithelium regeneration that produces hyperplastic crypts following injury; therefore, these organoids were designated hyperplastic intestinal organoids (Hyperorganoids). Single-cell RNA sequencing identified different regenerative stem cell populations in our Hyper-organoids that shared molecular features with in vivo injury-responsive Lgr5+ stem cells or Clu+ revival stem cells. Further analysis revealed that VPA and EPZ6438 were indispensable for epigenome reprogramming and regeneration in Hyper-organoids, which functioned through epigenetically regulating YAP signaling. Furthermore, VPA and EPZ6438 synergistically promoted regenerative response in gut upon damage in vivo. In summary, our results demonstrated a new in vitro organoid model to study epithelial regeneration, highlighting the importance of epigenetic reprogramming that pioneers tissue repair.
2021-01-16 | GSE164940 | GEO
Project description:We developed hepatic organoids (HOs) from embryonic stem cells (ESCs) through a de novo induction protocol, mimicking the stages of fetal liver development: ESCs to definitive endoderm (DE), then to foregut (FG), hepatoblasts (HB), and finally to HOs stage 1 (HO1), culminating in self-organizing HOs stage 2 (HO2) via dissociation and re-inoculation. Comprehensive transcriptomic and proteomic sequencing and analysis were conducted on FG, HB, HO1, and HO2.
| PXD054162 |
Project description:The capacity of 3D organoids to mimic physiological tissue organization and functionality has provided an invaluable tool to model development and disease in vitro. However, conventional organoid cultures primarily represent the homeostasis of self-organizing including VPA, EPZ6438, LDN193189, and R-Spondin 1 conditioned medium, which mimics the gut epithelium regeneration that produces hyperplastic crypts following injury; therefore, these organoids were designated hyperplastic intestinal organoids (Hyperorganoids). Single-cell RNA sequencing identified different regenerative stem cell populations in our Hyper-organoids that shared molecular features with in vivo injury-responsive Lgr5+ stem cells or Clu+ revival stem cells. Further analysis revealed that VPA and EPZ6438 were indispensable for epigenome reprogramming and regeneration in Hyper-organoids, which functioned through epigenetically regulating YAP signaling. Furthermore, VPA and EPZ6438 synergistically promoted regenerative response in gut upon damage in vivo. In summary, our results demonstrated a new in vitro organoid model to study epithelial regeneration, highlighting the importance of epigenetic reprogramming that pioneers tissue repair.
2021-01-20 | GSE165157 | GEO
Project description:The capacity of 3D organoids to mimic physiological tissue organization and functionality has provided an invaluable tool to model development and disease in vitro. However, conventional organoid cultures primarily represent the homeostasis of self-organizing including VPA, EPZ6438, LDN193189, and R-Spondin 1 conditioned medium, which mimics the gut epithelium regeneration that produces hyperplastic crypts following injury; therefore, these organoids were designated hyperplastic intestinal organoids (Hyperorganoids). Single-cell RNA sequencing identified different regenerative stem cell populations in our Hyper-organoids that shared molecular features with in vivo injury-responsive Lgr5+ stem cells or Clu+ revival stem cells. Further analysis revealed that VPA and EPZ6438 were indispensable for epigenome reprogramming and regeneration in Hyper-organoids, which functioned through epigenetically regulating YAP signaling. Furthermore, VPA and EPZ6438 synergistically promoted regenerative response in gut upon damage in vivo. In summary, our results demonstrated a new in vitro organoid model to study epithelial regeneration, highlighting the importance of epigenetic reprogramming that pioneers tissue repair.
2021-01-20 | GSE165092 | GEO
Project description:Human stem cell-based embryo-like models have opened new avenues of research into the principles of embryonic development using experimentally amenable in vitro systems. One of the benefits of embryo-like models over organoids is their multilineage differentiation, which allows the co-development of different populations and interaction between tissues. Here, we develop a method of generating somite- and neural tube-containing models, called human Trunk-like Structures (hTLS). These hTLS contain SOX2+ TBXT+ neuromesodermal progenitors, presomitic mesoderm, and somitic epithelial tissues, alongside a neural tube structure. As well as the expression of Wnt/FGF ligands posteriorly and Retinoic Acid (RA) pathway components anteriorly, we observe oscillatory HES7 expression, and show that increasing exposure to a Sonic Hedgehog signalling agonist (SAG) increasingly ventralises tissue identity. Additionally, we show that RA and noncanonical Wnt interactions likely occur between the somites and neural tube. In particular, we observe medially-localised ALDH1A2 expression in the somites - at the interface with the neural tube – which we validated in mouse embryos, whereas in somite-only structures, ALDH1A2 is anteroposteriorly polarised. This suggests that interactions between the neural tube and the somites might be responsible for mediolateral somitic organisation, both in vitro and in vivo, and highlights the value of embryo models to reveal insights into mammalian tissue co-development.
2025-10-01 | GSE268451 | GEO
Project description:Self-elongating neural tube organoids recapitulate key aspects of the morphology, anterior-posterior patterning, neural crest emergence and neural differentiation of mouse embryo in vivo by self-organization. We used single-cell RNA sequencing (scRNA-seq) to analyse the cell types and to reveal the sequence of transcriptional events in the emergence of neural crest cells and neural differentiation.
2022-10-12 | GSE214996 | GEO
Project description:Defining molecular controls that orchestrate human brain development is essential for uncovering the complexity behind neurodevelopment and the pathogenesis of neurological disorders. Due to the difficulties in accessing embryonic and fetal brain tissues, the differentiation of human pluripotent stem cell (hPSC)-derived three-dimensional neural organoids has made it possible to recapitulate this developmental process in vitro and provide a unique opportunity to investigate human brain development and disease. To elucidate the molecular programs that drive this highly dynamic process, here, we generate a comprehensive trans-omic map of the phosphoproteome, proteome, and transcriptome of the initial stages of pluripotency and neural differentiation towards the formation of cerebral organoids. Our integrative analysis uncovers key phospho-signalling events underlying neural lineage differentiation, and their convergence on transcriptional (co-)factors and chromatin remodellers that govern downstream gene regulatory networks (GRNs). Comparative analysis with developing human and mouse embryos using these GRNs demonstrates the fidelity of our early cerebral organoids in modelling embryonic brain development. Finally, we demonstrate biochemical modulation of the AKT signalling as a key molecular switch for controlling human cerebral organoid formation. Our data provides a comprehensive resource to gain insight into the molecular controls in human embryonic brain development and also provide a guide for future development of protocols for human cerebral organoid differentiation.
2024-04-23 | PXD047423 | Pride