ArticleStem cells translational medicine2021
Enhanced differentiation of human induced pluripotent stem cells toward the midbrain dopaminergic neuron lineage through GLYPICAN-4 downregulation.
Article in Stem cells translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations.Acta pharmaceutica Sinica. B · 2026Review
- Temporal expression dynamics of glypicans during hiPSC cardiac differentiation.Frontiers in cell and developmental biology · 2026Article
- Generation of Active Neurons from Mouse Embryonic Stem Cells Using Retinoic Acid and Purmorphamine.International journal of molecular sciences · 2025Article
- Evaluation of circulating glypican 4 as a novel biomarker in disease - A comprehensive review.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Article
- Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson's disease.Scientific reports · 2024Article
- Review
- Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-β protein sensing.Nature communications · 2023Article
- Review
- Enhanced differentiation of human induced pluripotent stem cells toward the midbrain dopaminergic neuron lineage through GLYPICAN-4 downregulation.Stem cells translational medicine · 2021Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Enhancing the differentiation potential of human induced pluripotent stem cells (hiPSC) into disease-relevant cell types is instrumental for their widespread application in medicine. Here, we show that hiPSCs downregulated for the signaling modulator GLYPICAN-4 (GPC4) acquire a new biological state characterized by increased hiPSC differentiation capabilities toward ventral midbrain dopaminergic (VMDA) neuron progenitors. This biological trait emerges both in vitro, upon exposing cells to VMDA neuronal differentiation signals, and in vivo, even when transplanting hiPSCs at the extreme conditions of floor-plate stage in rat brains. Moreover, it is compatible with the overall neuronal maturation process toward acquisition of substantia nigra neuron identity. HiPSCs with downregulated GPC4 also retain self-renewal and pluripotency in stemness conditions, in vitro, while losing tumorigenesis in vivo as assessed by flank xenografts. In conclusion, our results highlight GPC4 downregulation as a powerful approach to enhance generation of VMDA neurons. Outcomes may contribute to establish hiPSC lines suitable for translational applications.
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