AsianScientist (Aug. 12, 2015) – Researchers from the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences found that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules. Their results have been published in Cell Stem Cell.
Terminally differentiated somatic cells can be reprogrammed into pluripotent stem cells by forced expression of a specific set of transcription factors, indicating that cell fate determination is reversible. Furthermore, different combinations of lineage-specific transcription factors can bypass the pluripotent state, directly converting somatic cells into cardiomyocytes, hepatocytes or neurons, providing alternative avenues for disease modeling and regenerative medicine.
However, the introduction of ectopic transgenes limits their current therapeutic application. Thus, tightly controlled expression of ectopic genes and reducing the number of transcription factors have been tried.
A team of researchers led by Professor Pei Gang from the Chinese Academy of Sciences found that human fibroblasts were directly converted into neuronal cells by small molecules. Called chemical-induced neuronal cells (hciNs), the cells exhibited physiological properties like repetitive trains of action potential, fast inward sodium currents and spontaneous postsynaptic currents. Moreover, like hiPSC-derived neurons and TF-induced neurons, hciNs showed similar electrophysiological properties, including calcium transients.
To further characterize the genes expression signature, the researchers used the Fluidigm Biomark platform and microarray. Their results provided evidence that hciN cells were similar to that of TF-induced neurons or hiPSC-derived neurons, but different from the initial fibroblasts.
Team also used their chemical-induction protocol to generate Alzheimer’s disease patient fibroblast-derived neuronal cells for disease modeling.
Their findings indicate that this study present another strategy for generation of patient-specific neuronal cells, thus providing desirable neuron sources for personalized disease modeling or even potential cell replacement therapy for neurodegenerative diseases.
The article can be found at: Hu et al. (2015) Direct Conversion of Normal and Alzheimer’s Disease Human Fibroblasts into Neuronal Cells by Small Molecules.
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Source: Chinese Academy of Sciences; Photo: Shutterstock.
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