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On February 16th Stem Cell Reports published online a research paper by the Yan Gang Research Group of the Institute of Biochemistry and Cell Biology of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences, Direct Generation of Humane Neuro Cells from Adult Astrocytes by Small Molecules, reporting on the use of small molecular compound combinations to transform adult astrological glial cells directly into nerve cells.
astrological glial cells are the largest cell types in the brain, have the same progeny as neurons and proliferate when the brain is damaged, so they are considered the ideal starting cells for regenerating neurons.
previous studies have shown that exogenetic over-expression of specific transcription factors (e.g. NeuroD1, Sox2, etc.) can transform astrological glial cells into nerve cells in vitro and in the body, but the expression of these exogenetic genes is limited by the use of integrated viral vectors.
recent years, the use of permeable cells, biological effects reversible fine-tuning small molecular compounds to replace external transcription factors to achieve the transformation of cell fate has received more and more attention and application.
previously, the group had successfully converted mouse fibroblasts into neurogenic cells using specific combinations of small molecular compounds, as well as human fibroblasts and mouse as astrological glial cells into nerve cells.
Previously, it was reported that fetal astrological glial cells can be converted into nerve cells by a specific combination of compounds, and this study further demonstrates that adult glial cells with different characteristics than fetal astrological glial cells can also be converted into nerve cells by compound combinations under certain conditions.
these compound-induced nerve cells have the cell morphology of neurons, express neuron-specific genes, and have the electrophysiological activity of neurons.
further verified by transcriptional sequencing that the resulting nerve cells have a similar gene expression spectrum to those obtained by embryonic stem cell differentiation.
transplanted induced nerve cells into the brains of newborn mice, which can survive and mature.
these results prove that adult-sourced astrological glial cells can be induced into nerve cells, providing new ideas and strategies for neuronal regeneration.
The work was completed in cooperation with Shen Li, a professor at Zhejiang University, and received strong support from Fudan University Professor Yu Yongchun and Third Military Medical University Professor Yu Xiuwu, as well as financial support from the Ministry of Science and Technology, the Ministry of Education and other institutions, and technical support from the National Protein Science Research (Shanghai) facilities.
Diagram: Small molecular compounds induce adult astrocytes into nerve cells, and the resulting nerve cells have neuronal cell morphology, neuronal-specific genes, electrophysiological activity of neurons, and gene expression similar to those of nerve cells differentiated by embryonic stem cells.
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