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Conversion of human urine-derived cells into neuron-like cells by small molecules

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Abstract

Neural cell transplantation is an effective way for treatment of neurological diseases. However, the absence of transplantable human neurons remains a barrier for clinical therapies. Human urine-derived cells, namely renal cells and urine stem cells, have become a good source of cells for reprogramming or trans-differentiation research. Here, we show that human urine-derived cells can be partially converted into neuron-like cells by applying a cocktail of small molecules. Gene expression analysis has shown that these induced cells expressed some neuron-specific genes, and a proportion of the cells are GABAergic neurons. Moreover, whole-cell patch clamping recording has shown that some induced cells have neuron-specific voltage gated Na+ and K+ currents but have failed to generate Ca2+ currents and action potentials. Taken together, these results suggest that induced neuronal cells from human urine-derived cells may be useful for neurological disease modelling, drug screening and cell therapies.

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Acknowledgements

This work was supported by D&R Pharmaceutics China, University of South Australia (UniSA) Venture, UniSA International Research Tuition Scholarship (IRTS) scholarship and China Scholarship Council (CSC) Scholarship to Donghui Liu, and National Health and Medical Research Council (NHMRC) fellowship to Xin-Fu Zhou.

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Authors and Affiliations

  1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia

    Donghui Liu, Mohammed Al-Hawwas, Fiona Zhou, Larisa Bobrovskaya & Xin-Fu Zhou

  2. Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia

    Grigori Rychkov & Fiona Zhou

  3. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, 5000, Australia

    Grigori Rychkov & Fiona Zhou

  4. Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar

    Nimshitha Pavathuparambil Abdul Manaph

  5. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing, 210009, China

    Donghui Liu & Hong Liao

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  1. Donghui Liu
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  2. Grigori Rychkov
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  3. Mohammed Al-Hawwas
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  4. Nimshitha Pavathuparambil Abdul Manaph
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  6. Larisa Bobrovskaya
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  7. Hong Liao
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  8. Xin-Fu Zhou
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Contributions

DL: designed the experiments, performed the experiments, drafted the manuscript, read and approved the final manuscript. GR: collected, analyzed and interpreted the data, revised the manuscript, read and approved the final manuscript. MA-H: designed the experiments, collected, analyzed and interpreted the data, revised the manuscript, read and approved the final manuscript. NPAM: designed the experiments, revised the manuscript, read and approved the final manuscript. FZ: collected, analyzed and interpreted the data, revised the manuscript, read and approved the final manuscript. LB: revised the manuscript, read and approved the final manuscript. HL: supported and supervised the study, read and approved the final manuscript. X-FZ: designed the experiments, revised the manuscript, supported and supervised the study, read and approved the final manuscript.

Corresponding authors

Correspondence to Hong Liao or Xin-Fu Zhou.

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The authors declare that they have no conflict of interest.

Ethical approval

Human urine collection and storage were performed in accordance with University of South Australia Human Research Ethics (Ethics No.: 0000035945).

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Informed consent was obtained from all donors for being included in the study.

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Liu, D., Rychkov, G., Al-Hawwas, M. et al. Conversion of human urine-derived cells into neuron-like cells by small molecules. Mol Biol Rep 47, 2713–2722 (2020). https://doi.org/10.1007/s11033-020-05370-1

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  • DOI: https://doi.org/10.1007/s11033-020-05370-1

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