Parallel scRNA-seq and genetic recording reveals lineage decisions in early mouse embryogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA591948 | ENA |
REPOSITORIES: ENA
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Project description:How cell fate is specified at early stages of development is a fundamental question in biology. We apply deep transcriptomic profiling to map cell lineages at single cell resolution in embryoid bodies (EBs); a spontaneous, manipulatable, in vitro system for embryonic development. We predict the overall cell fate trajectory and define the transcriptomic landscape of cells at each critical branch. We present a dual barcoding system, comprising a static cellular barcode and inducible genetic recorder, and leverage long-read sequencing to obtain both barcodes and transcriptome from each single cell. Using this system, we confirm overall trajectory architecture, and validate key branch points, including the early isolation of the primordial germ cell (PGC) like lineage from preimplantation epiblast-like cells. Our data suggest DNA methylation is a critical determinant of PGC cell fate choice before the postimplantation epiblast cell state is determined. Together, our data provide a high resolution lineage decision map in an organoid model of early embryogenesis, with implications for the developing embryo.
2020-08-07 | GSE140890 | GEO
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Project description:Understanding the emergence of complex multicellular organisms from single totipotent cells, or ontogenesis, represents a foundational question in biology. The study of mammalian development is particularly challenging due to the difficulty of monitoring embryos in utero, the variability of progenitor field sizes, and the indeterminate relationship between the generation of uncommitted progenitors and their progression to subsequent stages. Here, we present a flexible, high information, multi-channel molecular recorder with a single cell (sc) readout and apply it as an evolving lineage tracer to define a mouse cell fate map from fertilization through gastrulation. By combining lineage information with scRNA-seq profiles, we recapitulate canonical developmental relationships between different tissue types and reveal an unexpected transcriptional convergence of endodermal cells from extra-embryonic and embryonic origins, illustrating how lineage information complements scRNA-seq to define cell types. Finally, we apply our cell fate map to estimate the number of embryonic progenitor cells and the degree of asymmetric partitioning within the pluripotent epiblast during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems to facilitate a quantitative framework for describing developmental processes.
2019-05-14 | GSE117542 | GEO
Project description:Gastrulation is a critical stage of embryonic development during which the three germ layers are established. Deciphering the molecular mechanisms underlying this proces from a protein perspective remains a significant challenge. To address this, we employed a multilayered mass spectrometry-based proteomics approach to investigate the global dynamics of (phospho)protein expression during differentiation of ESCs towards gastruloids – an in vitro model of gastrulation-stage embryogenesis. Our findings revealed that many proteins exhibited temporal expression with unique expression profiles corresponding to the three germ layers. Additionally, we profiled enhancer interaction landscapes in ESCs and gastruloids using p300 proximity labeling, which revealed numerous gastruloid-specific transcription factors and chromatin remodelers. Subsequent degron based perturbations combined with scRNA-seq revealed a critical role for Zeb2 in regulating mouse and human somitogenesis. Overall, this study provides a rich resource for developmental and synthetic biology communities endeavoring to understand mammalian embryogenesis.
2024-05-21 | PXD041309 | Pride
Project description:To study developmental trajectories in brain organoids, we conducted scRNA-seq and scATAC-seq in parallel on a dense timecourse of early development.
2022-08-18 | E-MTAB-12001 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7229772 | biostudies-literature
Project description:Gastrulation is a critical stage of embryonic development during which the three germ layers are established. Deciphering the molecular mechanisms underlying this proces from a protein perspective remains a significant challenge. To address this, we employed a multilayered mass spectrometry-based proteomics approach to investigate the global dynamics of (phospho)protein expression during differentiation of ESCs towards gastruloids – an in vitro model of gastrulation-stage embryogenesis. Our findings revealed that many proteins exhibited temporal expression with unique expression profiles corresponding to the three germ layers. Additionally, we profiled enhancer interaction landscapes in ESCs and gastruloids using p300 proximity labeling, which revealed numerous gastruloid-specific transcription factors and chromatin remodelers. Subsequent degron based perturbations combined with scRNA-seq revealed a critical role for Zeb2 in regulating mouse and human somitogenesis. Overall, this study provides a rich resource for developmental and synthetic biology communities endeavoring to understand mammalian embryogenesis.
2024-05-21 | GSE229028 | GEO
Project description:gnp07_regeneome_embryogenesis - embryogenesis col0 - Identify genes involved in somatic embryogenesis - compare embryogenic areas of a callus with undifferenciate area in the same callus
2012-06-01 | GSE30425 | GEO
Project description:gnp07_regeneome_embryogenesis - embryogenesis ws - Identify genes involved in somatic embryogenesis - To compare embryogenic areas of a callus with undifferenciate area in the same callus
2012-06-01 | GSE30383 | GEO
Project description:gnp07_regeneome_embryogenesis - embryogenesis col0 - Identify genes involved in somatic embryogenesis - compare embryogenic areas of a callus with undifferenciate area in the same callus 4 dye-swap - tissue comparison
2012-05-31 | E-GEOD-30425 | biostudies-arrayexpress