ArticleProceedings of the National Academy of Sciences of the United States of America2018
Transdifferentiation of human adult peripheral blood T cells into neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 91 citations in OpenAlex.
- Direct neuronal reprogramming: emerging therapeutic strategies for neurodegenerative disorders.Annals of medicine · 2026Review
- Therapeutic potential of astrocyte transdifferentiated neurons.Neural regeneration research · 2026Article
- Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.Open biology · 2025Review
- NEUROD1 efficiently converts peripheral blood cells into neurons with partial reprogramming by pluripotency factors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.Nature cell biology · 2025Article
- Monitoring Autophagy in Human Aging: Key Cell Models and Insights.Frontiers in bioscience (Landmark edition) · 2025Review
- Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Phospho-regulation of ASCL1-mediated chromatin opening during cellular reprogramming.Development (Cambridge, England) · 2024Article
- Neural crest precursors from the skin are the primary source of directly reprogrammed neurons.Stem cell reports · 2024Article
- Genome-wide screening reveals essential roles for HOX genes and imprinted genes during caudal neurogenesis of human embryonic stem cells.Stem cell reports · 2024Article
- Human tNeurons reveal aging-linked proteostasis deficits driving Alzheimer's phenotypes.Research square · 2024Article
- Functional genomics and small molecules in mitochondrial neurodevelopmental disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Alzheimer's disease and synapse Loss: What can we learn from induced pluripotent stem Cells?Journal of advanced research · 2023Review
- Insights and applications of direct neuronal reprogramming.Current opinion in genetics & development · 2023Review
- Small Molecules Temporarily Induce Neuronal Features in Adult Canine Dermal Fibroblasts.International journal of molecular sciences · 2023Article
- Somatic Cell Reprogramming for Nervous System Diseases: Techniques, Mechanisms, Potential Applications, and Challenges.Brain sciences · 2023Review
- Regeneration of the cerebral cortex by direct chemical reprogramming of macrophages into neuronal cells in acute ischemic stroke.Frontiers in cellular neuroscience · 2023Article
- Moving CNS axon growth and regeneration research into human model systems.Frontiers in neuroscience · 2023Review
- Dental-derived cells for regenerative medicine: stem cells, cell reprogramming, and transdifferentiation.Journal of periodontal & implant science · 2022Review
- Somatic Lineage Reprogramming.Cold Spring Harbor perspectives in biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Human cell models for disease based on induced pluripotent stem (iPS) cells have proven to be powerful new assets for investigating disease mechanisms. New insights have been obtained studying single mutations using isogenic controls generated by gene targeting. Modeling complex, multigenetic traits using patient-derived iPS cells is much more challenging due to line-to-line variability and technical limitations of scaling to dozens or more patients. Induced neuronal (iN) cells reprogrammed directly from dermal fibroblasts or urinary epithelia could be obtained from many donors, but such donor cells are heterogeneous, show interindividual variability, and must be extensively expanded, which can introduce random mutations. Moreover, derivation of dermal fibroblasts requires invasive biopsies. Here we show that human adult peripheral blood mononuclear cells, as well as defined purified T lymphocytes, can be directly converted into fully functional iN cells, demonstrating that terminally differentiated human cells can be efficiently transdifferentiated into a distantly related lineage. T cell-derived iN cells, generated by nonintegrating gene delivery, showed stereotypical neuronal morphologies and expressed multiple pan-neuronal markers, fired action potentials, and were able to form functional synapses. These cells were stable in the absence of exogenous reprogramming factors. Small molecule addition and optimized culture systems have yielded conversion efficiencies of up to 6.2%, resulting in the generation of >50,000 iN cells from 1 mL of peripheral blood in a single step without the need for initial expansion. Thus, our method allows the generation of sufficient neurons for experimental interrogation from a defined, homogeneous, and readily accessible donor cell population.
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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.