ArticleScience advances2025
Three-dimensional cell-cell interactions promote direct reprogramming of patient fibroblasts into functional and transplantable neurons.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Brain organoids as models of extracellular vesicle-mediated human neural communication.Neural regeneration research · 2026Article
- In Vivo Direct Reprogramming: Current Progress and Future Prospects from Mechanisms to Therapeutic Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026Review
- Dynamic Proteomic and Metabolomic Analysis Reveals Metabolic Reprogramming During Early Neuronal Transdifferentiation of Human Fibroblasts Driven by Forskolin.Current issues in molecular biology · 2026Article
- Distinct media requirements for dopaminergic neuron reprogramming from human glia and fibroblasts.Scientific reports · 2026Article
- [Research advances on the application of skin appendage organoids in wound repair].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026Review
- Direct neuronal reprogramming for neurological diseases: applications, translational Challenges, and future directions.Frontiers in neuroscience · 2026Review
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Authors and funding
13 authors.
Funding
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Abstract
Direct reprogramming of somatic cells into induced neurons (iNs) has become an attractive strategy for the generation of patient-specific neurons for disease modeling and regenerative neuroscience. To this end, adult human dermal fibroblasts (hDFs) present one of the most relevant cell sources. However, iNs generated from adult hDFs using two-dimensional cultures are difficult to maintain in vitro and face challenges in survival upon transplantation into the adult brain, thus imposing constraints on biomedical applications of iN technology. Here, we present a platform for direct in vitro reprogramming of adult hDFs inside three-dimensional suspension microcultures (3D-iNs). We show that the 3D environment favors neuronal over fibroblast cellular identity to yield more robust conversion into functional neurons with extended culturing span. The 3D reprogramming approach also provides a platform for fusion into induced assembloids. 3D-iNs can be gently harvested and transplanted into the adult rodent brain to reproducibly generate neuron-rich grafts, thus eliminating a major bottleneck in the direct reprogramming field.
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