ArticleBiochemical and biophysical research communications2019
Attenuation of PRRX2 and HEY2 enables efficient conversion of adult human skin fibroblasts to neurons.
Article in Biochemical and biophysical research communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 36 citations in OpenAlex.
- ASCL1 promotes nuclear shrinkage in transdifferentiation by suppressing NUP37.Stem cell reports · 2026Article
- Research progress of single cell RNA sequencing in nervous system.Molecular biology reports · 2025Review
- PRRX2 Regulates GLI2 to Promote Proliferation, Invasion, and Metastasis by Inhibiting Senescence via Hedgehog Signaling.Cancer science · 2025Article
- Single-Cell RNA-Seq Reveals the Pseudo-temporal Dynamic Evolution Characteristics of ADSCs to Neuronal Differentiation.Cellular and molecular neurobiology · 2024Article
- Upregulation of PRRX2 by silencing Marveld3 as a protective mechanism against radiation-induced ferroptosis in skin cells.Molecular medicine (Cambridge, Mass.) · 2024Article
- Genomic characteristics of adipose-derived stromal cells induced into neurons based on single-cell RNA sequencing.Heliyon · 2024Article
- Spinal-Specific Super Enhancer in Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- PTBP2 attenuation facilitates fibroblast to neuron conversion by promoting alternative splicing of neuronal genes.Stem cell reports · 2023Article
- CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis.Journal of experimental & clinical cancer research : CR · 2022Article
- Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson's disease.Stem cell reports · 2022Article
- Generation of Induced Dopaminergic Neurons from Human Fetal Fibroblasts.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Benlysta-Loaded Sodium Alginate Hydrogel and Its Selective Functions in Promoting Skin Cell Growth and Inhibiting Inflammation.ACS omega · 2020Article
- Toward Generating Subtype-Specific Mesencephalic Dopaminergic NeuronsFrontiers in cell and developmental biology · 2020Review
- Next-generation disease modeling with direct conversion: a new path to old neurons.FEBS letters · 2019Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The direct conversion of accessible cells such as human fibroblasts to inaccessible cells, particularly neurons, opens up many opportunities for using the human model system to study diseases and discover therapies. Previous studies have indicated that the neuronal conversion of adult human skin fibroblasts is much harder than that for human lung fibroblasts, which are used in many experiments. Here we formally report this differential plasticity of human skin versus lung fibroblasts in their transdifferentiation to induced neurons. Using RNAseq of isogenic and non-isogenic pairs of human skin and lung fibroblasts at different days in their conversion to neurons, we found that several master regulators (TWIST1, TWIST2, PRRX1 and PRRX2) in the fibroblast Gene Regulatory Network were significantly downregulated in lung fibroblasts, but not in skin fibroblasts. By knocking down each of these genes and other genes that suppress the neural fate, such as REST, HES1 and HEY2, we found that the combined attenuation of HEY2 and PRRX2 significantly enhanced the transdifferentiation of human skin fibroblasts induced by ASCL1 and p53 shRNA. The new method, which overexpressed ASCL1 and knocked down p53, HEY2 and PRRX2 (ApH2P2), enabled the efficient transdifferentiation of adult human skin fibroblasts to MAP2
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