ArticleDevelopmental biology2013
BMP and TGF-β pathway mediators are critical upstream regulators of Wnt signaling during midbrain dopamine differentiation in human pluripotent stem cells.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data.PloS one · 2016Trial
- Non-cell autonomous downregulation of the purinergic receptor P2Y1R promotes neuroprotection after ischemic injury.Frontiers in cellular neuroscience · 2026Article
- Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons.Neural regeneration research · 2024Article
- TGFβ3, dibutyryl cAMP and a notch inhibitor modulate phenotype late in stem cell-derived dopaminergic neuron maturation.Frontiers in cell and developmental biology · 2023Article
- Efficient induction of neural progenitor cells from human ESC/iPSCs on Type I Collagen.Science China. Life sciences · 2021Article
- On the Road from Phenotypic Plasticity to Stem Cell Therapy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- TGFβ and Wnt Signaling Pathways Cooperatively Enhance Early Dopaminergic Differentiation of the Unrestricted Somatic Stem Cells.Journal of molecular neuroscience : MN · 2020Article
- Article
- Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells.Journal of developmental biology · 2019Review
- The versatility of RhoA activities in neural differentiation.Small GTPases · 2019Article
- Profiling of Argonaute-2-loaded microRNAs in a mouse model of frontotemporal dementia with parkinsonism-17.International journal of physiology, pathophysiology and pharmacology · 2018Article
- Opposite Roles of Wnt7a and Sfrp1 in Modulating Proper Development of Neural Progenitors in the Mouse Cerebral Cortex.Frontiers in molecular neuroscience · 2018Article
- Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation.Scientific reports · 2017Article
- Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies.Journal of visualized experiments : JoVE · 2017Article
- Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation.Molecular cell · 2017Article
- Effects of Feeder Cells on Dopaminergic Differentiation of Human Embryonic Stem Cells.Frontiers in cellular neuroscience · 2016Article
- Transcriptomic Analysis of Purified Embryonic Neural Stem Cells from Zebrafish Embryos Reveals Signaling Pathways Involved in Glycine-Dependent Neurogenesis.Frontiers in molecular neuroscience · 2016Article
- Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons.Nature communications · 2015Article
- A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells.Scientific reports · 2015Article
- miR-135 family members mediate podocyte injury through the activation of Wnt/β-catenin signaling.International journal of molecular medicine · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Although many laboratories currently use small molecule inhibitors of the BMP (Dorsomorphin/DM) and TGF-β (SB431542/SB) signaling pathways in protocols to generate midbrain dopamine (mDA) neurons from hES and hiPS cells, until now, these substances have not been thought to play a role in the mDA differentiation process. We report here that the transient inhibition of constitutive BMP (pSMADs 1, 5, 8) signaling, either alone or in combination with TGF-β inhibition (pSMADs 2, 3), is critically important in the upstream regulation of Wnt1-Lmx1a signaling in mDA progenitors. We postulate that the mechanism via which DM or DM/SB mediates these effects involves the up-regulation in SMAD-interacting protein 1 (SIP1), which results in greater repression of the Wnt antagonist, secreted frizzled related protein 1 (Sfrp1) in stem cells. Accordingly, knockdown of SIP1 reverses the inductive effects of DM/SB on mDA differentiation while Sfrp1 knockdown/inhibition mimics DM/SB. The rise in Wnt1-Lmx1a levels in SMAD-inhibited cultures is, however, accompanied by a reciprocal down-regulation in SHH-Foxa2 levels leading to the generation of few TH+ neurons that co-express Foxa2. If however, exogenous SHH/FGF8 is added along with SMAD inhibitors, equilibrium in these two important pathways is achieved such that authentic (Lmx1a+Foxa2+TH+) mDA neuron differentiation is promoted while alternate cell fates are suppressed in stem cell cultures. These data indicate that activators/inhibitors of BMP and TGF-β signaling play a critical upstream regulatory role in the mDA differentiation process in human pluripotent stem cells.
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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.