ArticlePLoS computational biology2021
A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Signaling Pathways in Human Blastocyst Development: From Molecular Mechanisms to In Vitro Optimization.Journal of developmental biology · 2025Review
- Generative model for the first cell fate bifurcation in mammalian development.Development (Cambridge, England) · 2025Article
- Self-organization of mouse embryonic stem cells into reproducible pre-gastrulation embryo models via CRISPRa programming.Cell stem cell · 2025Article
- Origin, fate and function of extraembryonic tissues during mammalian development.Nature reviews. Molecular cell biology · 2025Review
- From sampling to simulating: Single-cell multiomics in systems pathophysiological modeling.iScience · 2024Review
- AI-powered simulation-based inference of a genuinely spatial-stochastic gene regulation model of early mouse embryogenesis.PLoS computational biology · 2024Article
- Self-organization of embryonic stem cells into a reproducible embryo model through epigenome editing.bioRxiv : the preprint server for biology · 2024Article
- Biophysical models of early mammalian embryogenesis.Stem cell reports · 2023Review
- Multiscale modeling of drug resistance in glioblastoma with gene mutations and angiogenesis.Computational and structural biotechnology journal · 2023Article
- Journey of the mouse primitive endoderm: from specification to maturation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Initial source of heterogeneity in a model for cell fate decision in the early mammalian embryo.Interface focus · 2022Article
- A computational model of organism development and carcinogenesis resulting from cells' bioelectric properties and communication.Scientific reports · 2022Article
- How a cell decides its own fate: a single-cell view of molecular mechanisms and dynamics of cell-type specification.Biochemical Society transactions · 2021Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
During early mammalian embryo development, a small number of cells make robust fate decisions at particular spatial locations in a tight time window to form inner cell mass (ICM), and later epiblast (Epi) and primitive endoderm (PE). While recent single-cell transcriptomics data allows scrutinization of heterogeneity of individual cells, consistent spatial and temporal mechanisms the early embryo utilize to robustly form the Epi/PE layers from ICM remain elusive. Here we build a multiscale three-dimensional model for mammalian embryo to recapitulate the observed patterning process from zygote to late blastocyst. By integrating the spatiotemporal information reconstructed from multiple single-cell transcriptomic datasets, the data-informed modeling analysis suggests two major processes critical to the formation of Epi/PE layers: a selective cell-cell adhesion mechanism (via EphA4/EphrinB2) for fate-location coordination and a temporal attenuation mechanism of cell signaling (via Fgf). Spatial imaging data and distinct subsets of single-cell gene expression data are then used to validate the predictions. Together, our study provides a multiscale framework that incorporates single-cell gene expression datasets to analyze gene regulations, cell-cell communications, and physical interactions among cells in complex geometries at single-cell resolution, with direct application to late-stage development of embryogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.