ArticleMolecular biology of the cell2014
Primary cilia in stem cells and neural progenitors are regulated by neutral sphingomyelinase 2 and ceramide.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- Ciliary Membrane Lipid Homeostasis in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The primary cilium at the helm: gatekeeper of TGF-β superfamily signaling in development, homeostasis, and disease.Biochemical Society transactions · 2026Review
- Primary cilia promote resistance to EGFR tyrosine kinase inhibitor, osimertinib, in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2026Article
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development.Journal of neurochemistry · 2025Review
- Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model.Nature communications · 2025Article
- Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.The Journal of cell biology · 2025Article
- Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease.Current opinion in neurobiology · 2025Review
- SMPD4-mediated sphingolipid metabolism regulates brain and primary cilia development.Development (Cambridge, England) · 2024Article
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles.Journal of extracellular vesicles · 2024Article
- Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.International journal of molecular sciences · 2024Review
- Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model.Cells · 2023Article
- Mass spectrometry imaging as an emerging tool for studying metabolism in human brain organoids.Frontiers in molecular biosciences · 2023Article
- Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling.Molecular metabolism · 2022Review
- Ceramide/Sphingosine 1-Phosphate Axis as a Key Target for Diagnosis and Treatment in Alzheimer's Disease and Other Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Sphingolipids in embryonic development, cell cycle regulation, and stemness - Implications for polyploidy in tumors.Seminars in cancer biology · 2022Review
- TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling.Cell reports · 2022Article
- Extracellular vesicles and immunogenic stress in cancer.Cell death & disease · 2021Review
- Stem cells' centrosomes: How can organelles identified 130 years ago contribute to the future of regenerative medicine?World journal of stem cells · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We show here that human embryonic stem (ES) and induced pluripotent stem cell-derived neuroprogenitors (NPs) develop primary cilia. Ciliogenesis depends on the sphingolipid ceramide and its interaction with atypical PKC (aPKC), both of which distribute to the primary cilium and the apicolateral cell membrane in NP rosettes. Neural differentiation of human ES cells to NPs is concurrent with a threefold elevation of ceramide-in particular, saturated, long-chain C16:0 ceramide (N-palmitoyl sphingosine) and nonsaturated, very long chain C24:1 ceramide (N-nervonoyl sphingosine). Decreasing ceramide levels by inhibiting ceramide synthase or neutral sphingomyelinase 2 leads to translocation of membrane-bound aPKC to the cytosol, concurrent with its activation and the phosphorylation of its substrate Aurora kinase A (AurA). Inhibition of aPKC, AurA, or a downstream target of AurA, HDAC6, restores ciliogenesis in ceramide-depleted cells. Of importance, addition of exogenous C24:1 ceramide reestablishes membrane association of aPKC, restores primary cilia, and accelerates neural process formation. Taken together, these results suggest that ceramide prevents activation of HDAC6 by cytosolic aPKC and AurA, which promotes acetylation of tubulin in primary cilia and, potentially, neural processes. This is the first report on the critical role of ceramide generated by nSMase2 in stem cell ciliogenesis and differentiation.
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