ArticleGenome biology2016
Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers, 1 of them a synthesis that pooled it.
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Who cites it
263 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.International journal of molecular sciences · 2022Pooled it
- CauTrigger: deciphering biological system state transitions by hierarchical causal decomposition.Nature methods · 2026Article
- scCADI: Cell-Aware Diffusion Model for Single-Cell RNA-seq Imputation.Interdisciplinary sciences, computational life sciences · 2026Article
- scASprofiler: profiling single-cell RNA splicing with a deep convolutional generative network.Briefings in bioinformatics · 2026Article
- Single-cell marker gene clustering: A unified deep learning framework for marker gene-based clustering of single-cell RNA-sequencing data.Quantitative biology (Beijing, China) · 2026Article
- IAGRN: An Interleaved-Attention Graph Neural Network for Gene Regulatory Network Inference.International journal of molecular sciences · 2026Article
- Article
- Deep learning models for cell cycle phase prediction from single-cell RNA sequencing data.Briefings in bioinformatics · 2026Article
- HNPP: Higher-order network-based personalized PageRank for detecting critical phase in complex biological systems.PLoS computational biology · 2026Article
- Inferring cell-specific gene regulatory networks based on causal graph embedding.Cell reports methods · 2026Article
- From time-course expression to gene regulation: direct linear ODE inference without finite-difference approximation.bioRxiv : the preprint server for biology · 2026Article
- Inferring stochastic dynamics by biophysical Neural ODE using single-cell transcriptomics.Nature communications · 2026Article
- PSGRN: Gene regulatory network inference from single-cell perturbational data through self-training with synthetic gold standards.Science advances · 2026Article
- AutoGERN: single-cell RNA-seq gene regulatory network inference via explicit link modeling and adaptive architectures.Bioinformatics (Oxford, England) · 2026Article
- Unveiling gene perturbation effects through gene regulatory networks inference from single-cell transcriptomic data.PLoS computational biology · 2026Article
- The diploid reference genome of a human embryonic stem cell line.bioRxiv : the preprint server for biology · 2026Article
- scZiva: imputation method for single-cell RNA-seq data with zero-inflated variational autoencoder.BMC bioinformatics · 2026Article
- GDSim: accurate simulation for single-cell transcriptomes based on the guided diffusion model.Briefings in bioinformatics · 2026Article
- Impacts of Oxygen Tension on Developmental Competence of Preimplantation Embryos.Biomolecules · 2026Review
- scLong: a billion-parameter foundation model for capturing long-range gene context in single-cell transcriptomics.Nature communications · 2026Article
203 more citing papers are in PubMed but not listed here.
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10 authors.
Funding
Abstract
backgroundHuman pluripotent stem cells offer the best available model to study the underlying cellular and molecular mechanisms of human embryonic lineage specification. However, it is not fully understood how individual stem cells exit the pluripotent state and transition towards their respective progenitor states.
resultsHere, we analyze the transcriptomes of human embryonic stem cell-derived lineage-specific progenitors by single-cell RNA-sequencing (scRNA-seq). We identify a definitive endoderm (DE) transcriptomic signature that leads us to pinpoint a critical time window when DE differentiation is enhanced by hypoxia. The molecular mechanisms governing the emergence of DE are further examined by time course scRNA-seq experiments, employing two new statistical tools to identify stage-specific genes over time (SCPattern) and to reconstruct the differentiation trajectory from the pluripotent state through mesendoderm to DE (Wave-Crest). Importantly, presumptive DE cells can be detected during the transitory phase from Brachyury (T) (+) mesendoderm toward a CXCR4 (+) DE state. Novel regulators are identified within this time window and are functionally validated on a screening platform with a T-2A-EGFP knock-in reporter engineered by CRISPR/Cas9. Through loss-of-function and gain-of-function experiments, we demonstrate that KLF8 plays a pivotal role modulating mesendoderm to DE differentiation.
conclusionsWe report the analysis of 1776 cells by scRNA-seq covering distinct human embryonic stem cell-derived progenitor states. By reconstructing a differentiation trajectory at single-cell resolution, novel regulators of the mesendoderm transition to DE are elucidated and validated. Our strategy of combining single-cell analysis and genetic approaches can be applied to uncover novel regulators governing cell fate decisions in a variety of systems.
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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 OpenQuestion graph.