Tracking Early Mammalian Organogenesis – Prediction and Validation of Differentiation Trajectories at Whole Organism Scale
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PROVIDER: PRJEB53140 | ENA |
REPOSITORIES: ENA
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Project description:Tracking Early Mammalian Organogenesis – Prediction and Validation of Differentiation Trajectories at Whole Organism Scale (Complementary data)
| PRJEB71858 | ENA
Project description:This project is based on the extension of the single cell transcriptomics atlas of mouse development towards E9.5. Inference of cell differentiation trajectories was carried out using Waddington-Optimal Transport, and the resulting computational reconstruction was contrasted with grafting experiments as well as complementary scRNA-seq experiments.
2023-01-01 | E-MTAB-11763 | biostudies-arrayexpress
Project description:This project is based on the extension of the single cell transcriptomics atlas of mouse development towards E9.5. Inference of cell differentiation trajectories was carried out using Waddington-Optimal Transport, and the resulting computational reconstruction was contrasted with grafting experiments as well as complementary scRNA-seq experiments. This data submission refers to the grafting experiments.
2024-01-31 | E-MTAB-13645 | biostudies-arrayexpress
Project description:Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 in 6-h intervals and combined this new dataset with our previous atlas (E6.5-E8.5) to produce a densely sampled timecourse of >400,000 cells from early gastrulation to organogenesis. Computational lineage reconstruction identified complex waves of blood and endothelial development, including a new programme for somite-derived endothelium. We also dissected the E7.5 primitive streak into four adjacent regions, performed scRNA-seq and predicted cell fates computationally. Finally, we defined developmental state/fate relationships by combining orthotopic grafting, microscopic analysis and scRNA-seq to transcriptionally determine cell fates of grafted primitive streak regions after 24 h of in vitro embryo culture. Experimentally determined fate outcomes were in good agreement with computationally predicted fates, demonstrating how classical grafting experiments can be revisited to establish high-resolution cell state/fate relationships. Such interdisciplinary approaches will benefit future studies in developmental biology and guide the in vitro production of cells for organ regeneration and repair.
| S-EPMC10906099 | biostudies-literature
Project description:During mammalian organogenesis, the cells of the three germ layers transform into an embryo that includes most major internal and external organs. The key regulators of developmental defects can be studied during this crucial period, but conventional approaches lack the throughput and resolution to obtain a global view of the molecular states and trajectories of a rapidly diversifying and expanding number of cell types. Here we set out to investigate the transcriptional dynamics of mouse development during organogenesis at single cell resolution. With an improved single cell combinatorial indexing-based protocol (‘sci-RNA-seq3’), we profiled over 2 million cells derived from 61 mouse embryos staged between 9.5 and 13.5 days of gestation (E9.5 to E13.5; 10 to 15 replicates per timepoint). We identify hundreds of expanding, contracting and transient cell types, many of which are only detected because of the depth of cellular coverage obtained here, and define the corresponding sets of cell type-specific marker genes, several of which we validate by whole mount in situ hybridization. We explore the dynamics of proliferation and gene expression within cell types over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle. With a new algorithm (Monocle 3), we identify the major single cell developmental trajectories of mouse organogenesis, and within these discover examples of distinct paths to the same endpoint, i.e. branching and convergence. These data comprise a foundational resource for mammalian developmental biology, and are made available in a way that will facilitate their ongoing annotation by the research community.
2019-02-20 | GSE119945 | GEO
Project description:Immune cells sense their environment and adapt their state. Deciphering cellular trajectories unfolding over time is fundamental for understanding biology. Empirical in vivo genomic technologies measuring both cell state and time are lacking. Here, we present Zman-seq, a single-cell technology tracking transcriptomic dynamics across time by introducing fluorescent time stamps into immune cells. We applied Zman-seq to resolve immune cell state-transitions of the dysfunctional tumor immune microenvironment (TME) of glioblastoma (GBM). By measuring the exposure time of infiltrating immune cells in the TME, Zman-seq defines the cellular and molecular trajectories underlying immune incompetence in GBM. Within 24 hours, cytotoxic NK cells transitioned to a dysfunctional program regulated by Tgfb1, while monocytes differentiated into immunosuppressive macrophages in 36-48 hours. Anti-TREM2 antagonistic antibody reshaped the TME by redirecting monocytes to pro-inflammatory macrophages. Zman-seq is a broadly applicable technology enabling empirical measurements of differentiation trajectories guiding the development of more efficacious immunotherapies.
2023-12-21 | GSE232040 | GEO
Project description:Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. We report the generation of human trunk-like structures that model the co-morphogenesis, patterning, and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into neural tubes surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis.
2023-08-31 | GSE215982 | GEO
Project description:Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. We report the generation of human trunk-like structures that model the co-morphogenesis, patterning, and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into neural tubes surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis.
2023-08-31 | GSE215981 | GEO
Project description:N6-methyladenosine (m6A) in mRNA is key to eukaryotic gene regulation. Many m6A functions involve RNA-binding proteins that recognize m6A via a YT521-B Homology (YTH) domain. YTH domain proteins contain long intrinsically disordered regions (IDRs) that may mediate phase separation and interaction with protein partners, but whose precise biochemical functions remain largely unknown. The Arabidopsis thaliana YTH domain proteins ECT2, ECT3 and ECT4 accelerate organogenesis through stimulation of cell division in organ primordia. Here, we use ECT2 to reveal molecular underpinnings of this function. We show that stimulation of leaf formation requires the long N-terminal IDR, and we identify two short IDR-elements required for ECT2-mediated organogenesis. Of these two, a 19-amino acid region containing a tyrosine-rich motif conserved in both plant and metazoan YTHDF proteins is necessary for binding to the major cytoplasmic poly(A)-binding proteins PAB2, PAB4 and PAB8. Remarkably, overexpression of PAB4 in leaf primordia partially rescues the delayed leaf formation in ect2 ect3 ect4 mutants, suggesting that the ECT2-PAB2/4/8 interaction on target mRNAs of organogenesis-related genes may overcome limiting PAB concentrations in primordial cells.
2023-11-28 | PXD045801 | Pride
Project description:Prediction and validation of a human immunodeficiency with CRISPR
| PRJNA1028553 | ENA