ArticleExperimental & molecular medicine2018
Wnt signal activation induces midbrain specification through direct binding of the beta-catenin/TCF4 complex to the EN1 promoter in human pluripotent stem cells.
Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Combining in vitro and in silico approaches to model neural tube patterning and isthmic organizer formation.NPJ systems biology and applications · 2026Article
- Integrated Single-cell Analysis Uncovers Regulatory Logic of Cranial Ectoderm Development.bioRxiv : the preprint server for biology · 2025Article
- Acetylation of lysine 49 on Ctnnb1 drives naïve pluripotency in murine stem cells by modulating Nanog function.PNAS nexus · 2025Article
- AUTS2 disruption causes neuronal differentiation defects in human cerebral organoids through hyperactivation of the WNT/β-catenin pathway.Scientific reports · 2024Article
- Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons.International journal of molecular sciences · 2022Review
- From Causal Networks to Adverse Outcome Pathways: A Developmental Neurotoxicity Case Study.Frontiers in toxicology · 2022Article
- Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson's disease-linkedScience advances · 2021Article
- T-Cell Factors as Transcriptional Inhibitors: Activities and Regulations in Vertebrate Head Development.Frontiers in cell and developmental biology · 2021Review
- Toward Spatial Identities in Human Brain Organoids-on-Chip Induced by Morphogen-Soaked Beads.Bioengineering (Basel, Switzerland) · 2020Article
- Neuronal Reprogramming for Tissue Repair and Neuroregeneration.International journal of molecular sciences · 2020Review
- TIMP-1 inhibits proliferation and osteogenic differentiation of hBMSCs through Wnt/β-catenin signaling.Bioscience reports · 2019Article
- Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells.Journal of developmental biology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs). The EN1 promoter region contains a putative TCF4-binding site that directly interacts with the β-catenin/TCF complex upon Wnt signal activation. Once differentiated, NPCs treated with a Wnt signal agonist gave rise to functional midbrain neurons including glutamatergic, GABAergic, and DA neurons. Our results provide a potential molecular mechanism that underlies midbrain specification of human PSC-derived NPCs by Wnt activation, as well as a differentiation paradigm for generating human midbrain neurons that may serve as a cellular platform for studying the ontogenesis of midbrain neurons and neurological diseases relevant to the midbrain.
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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.