ArticleNature metabolism2020
Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- ProtectiveiScience · 2026Article
- Predictive control of human pancreatic cell fate using a digital model ofbioRxiv : the preprint server for biology · 2026Article
- Stem cell therapies for treatment of diabetes mellitus.Chinese medical journal · 2026Review
- Modeling immune responses to autologous and allogeneic human stem cell-derived islet grafts in vivo.JCI insight · 2026Article
- Divergent cell-type specific hypoxia responses in human stem cell-derived and primary islets.Scientific reports · 2026Article
- Bioengineering Pancreatic Organoids and iPSC-Derived β-Cells for Diabetes: Materials, Devices, and Translational Challenges.Bioengineering (Basel, Switzerland) · 2026Review
- Depolymerizing F-actin accelerates the exit from pluripotency to enhance stem cell-derived islet differentiation.Nature communications · 2026Article
- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
- Single-Cell Multi-Omics in Type 2 Diabetes Mellitus: Revealing Cellular Heterogeneity and Mechanistic Insights.International journal of molecular sciences · 2025Review
- Coxsackievirus B infection invokes unique cell-type-specific responses in primary human pancreatic islets.Cell reports · 2025Article
- Advances in Cell Replacement Therapies for Diabetes.Diabetes · 2025Review
- FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction.Nature communications · 2025Article
- The expression order determines the pioneer functions of NGN3 and NEUROD1 in pancreatic endocrine differentiation.Science advances · 2025Article
- ETVs dictate hPSC differentiation by tuning biophysical properties.Nature communications · 2025Article
- Mechanistic elucidation of human pancreatic acinar development using single-cell transcriptome analysis on a human iPSC differentiation model.Scientific reports · 2025Article
- Extracellular matrix proteins refine microenvironments for pancreatic organogenesis from induced pluripotent stem cell differentiation.Theranostics · 2025Article
- Dysregulated autophagy at the nexus of type 2 diabetes mellitus and pancreatic cancer pathogenesis.Frontiers in endocrinology · 2025Review
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- Deletion of RFX6 impairs iPSC-derived islet organoid development and survival, with no impact on PDX1Diabetologia · 2024Article
- mThe EMBO journal · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The in vitro differentiation of insulin-producing beta-like cells can model aspects of human pancreatic development. Here, we generate 95,308 single-cell transcriptomes and reconstruct a lineage tree of the entire differentiation process from human embryonic stem cells to beta-like cells to study temporally regulated genes during differentiation. We identify so-called 'switch genes' at the branch point of endocrine/non-endocrine cell fate choice, revealing insights into the mechanisms of differentiation-promoting reagents, such as NOTCH and ROCKII inhibitors, and providing improved differentiation protocols. Over 20% of all detectable genes are activated multiple times during differentiation, even though their enhancer activation is usually unimodal, indicating extensive gene reuse driven by different enhancers. We also identify a stage-specific enhancer at the TCF7L2 locus for diabetes, uncovered by genome-wide association studies, that drives a transient wave of gene expression in pancreatic progenitors. Finally, we develop a web app to visualize gene expression on the lineage tree, providing a comprehensive single-cell data resource for researchers studying islet biology and diabetes.
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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 OpenQuestion graph.