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Written | edited by xiao xia | typeset by Wang Duoyu | Hydrographic glioma is the most common primary brain tumor in adults
.
Among them, glioblastomas (GBM) are highly aggressive, which makes them difficult to cure
.
GBM will rapidly progress to the late stage in a short period of time, and the survival rate of patients is often very low, with a median survival time of only 15 months
.
At present, surgical resection and postoperative concurrent radiotherapy and chemotherapy are the main treatment methods, but their effects are limited
.
And immunotherapy, such as CAR-T or PD-1/PD-L1 therapy, cannot completely kill or remove glioma cells from the body
.
Therefore, there is an urgent need to find alternative treatments for GBM
.
GBM is caused by the uncontrolled division of glial cells, which nourish neurons and form the supporting matrix of brain tissue
.
Unlike neurons that do not divide, glial cells can undergo cell division, making them prone to form tumors
.
Studies have reported that ectopic expression of neural transcription factors can transform glial cells into neurons, which provides the possibility of transforming glioma cells
.
In March 2021, a research team led by Dr.
Chen Gong, director of the Brain Repair Center of Jinan University in China, published a research paper titled: Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion in Cancer Biology & Medicine
.
The research has developed a new type of gene therapy that can reprogram glioma cells into functional neurons, providing new ideas for the treatment of gliomas
.
The research developed a new cell reprogramming strategy, which converts proliferative glioma cells into non-proliferative neurons by overexpressing a single neural transcription factor NeuroD1, Neurog2 or Ascl1 in GBM tumor cells.
Cell transformation technology provides an alternative therapy for the treatment of brain tumors
.
The research team previously discovered that overexpression of the neural transcription factor NeuroD1 can convert astrocytes into neurons
.
NeuroD1, Neurog2 and Ascl1 belong to the basic helix-loop-helix (bHLH) family of neural transcription factors, and play a key role in the neural differentiation induction process of early brain development
.
The research team further tested the possibility of using neural transcription factors to convert glioma cells into neurons
.
After overexpressing Neurog2 or NeuroD1 in GBM cell lines, they found that most GBM cells showed neuronal morphology and expressed immature neuronal markers
.
At 30 days after infection, mature neuronal markers were detected in Neurog2-, NeuroD1-, or Ascl1-infected cells
.
Next, the research team characterized the transformed neuron subtypes based on the released neurotransmitters, especially glutamatergic and GABAergic neurons, which are the main excitatory and inhibitory neurons in the brain, respectively
.
Most of the neurons converted by Neurog2 or NeuroD1 are forebrain glutamatergic neurons, and Ascl1 shows a tendency to generate GABAergic neurons
.
Therefore, the expression of different transcription factors will have a significant impact on the transformed neuron subtypes
.
The research team observed from RNA sequencing analysis that these differences are also accompanied by different gene expression patterns of different neuronal subtypes
.
Next, they evaluated the cellular and functional characteristics of the transformed glioma cells
.
It is worth noting that these transformed cells show an arrangement of intracellular organelles similar to neurons, and to a certain extent exhibit neuronal signal transmission activities
.
To verify their findings in vivo, the research team injected retroviruses expressing the above factors into the brains of mice transplanted with GBM cells
.
The results showed that GBM cells effectively transformed into mouse neuronal cells, as evidenced by the expression of neuronal biomarkers
.
In addition, cell transformation also significantly inhibited the proliferation of these cancer cells in animals
.
Together, these findings indicate that the reprogramming of glioma cells into neuron-type cells provides a promising therapeutic strategy that can slow the growth of glioblastoma
.
This targeted approach can also help overcome the harmful side effects of conventional anti-cancer treatments on healthy brain cells
.
Original link: http:// Open for reprinting, welcome to forward to Moments and WeChat groups
.
Among them, glioblastomas (GBM) are highly aggressive, which makes them difficult to cure
.
GBM will rapidly progress to the late stage in a short period of time, and the survival rate of patients is often very low, with a median survival time of only 15 months
.
At present, surgical resection and postoperative concurrent radiotherapy and chemotherapy are the main treatment methods, but their effects are limited
.
And immunotherapy, such as CAR-T or PD-1/PD-L1 therapy, cannot completely kill or remove glioma cells from the body
.
Therefore, there is an urgent need to find alternative treatments for GBM
.
GBM is caused by the uncontrolled division of glial cells, which nourish neurons and form the supporting matrix of brain tissue
.
Unlike neurons that do not divide, glial cells can undergo cell division, making them prone to form tumors
.
Studies have reported that ectopic expression of neural transcription factors can transform glial cells into neurons, which provides the possibility of transforming glioma cells
.
In March 2021, a research team led by Dr.
Chen Gong, director of the Brain Repair Center of Jinan University in China, published a research paper titled: Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion in Cancer Biology & Medicine
.
The research has developed a new type of gene therapy that can reprogram glioma cells into functional neurons, providing new ideas for the treatment of gliomas
.
The research developed a new cell reprogramming strategy, which converts proliferative glioma cells into non-proliferative neurons by overexpressing a single neural transcription factor NeuroD1, Neurog2 or Ascl1 in GBM tumor cells.
Cell transformation technology provides an alternative therapy for the treatment of brain tumors
.
The research team previously discovered that overexpression of the neural transcription factor NeuroD1 can convert astrocytes into neurons
.
NeuroD1, Neurog2 and Ascl1 belong to the basic helix-loop-helix (bHLH) family of neural transcription factors, and play a key role in the neural differentiation induction process of early brain development
.
The research team further tested the possibility of using neural transcription factors to convert glioma cells into neurons
.
After overexpressing Neurog2 or NeuroD1 in GBM cell lines, they found that most GBM cells showed neuronal morphology and expressed immature neuronal markers
.
At 30 days after infection, mature neuronal markers were detected in Neurog2-, NeuroD1-, or Ascl1-infected cells
.
Next, the research team characterized the transformed neuron subtypes based on the released neurotransmitters, especially glutamatergic and GABAergic neurons, which are the main excitatory and inhibitory neurons in the brain, respectively
.
Most of the neurons converted by Neurog2 or NeuroD1 are forebrain glutamatergic neurons, and Ascl1 shows a tendency to generate GABAergic neurons
.
Therefore, the expression of different transcription factors will have a significant impact on the transformed neuron subtypes
.
The research team observed from RNA sequencing analysis that these differences are also accompanied by different gene expression patterns of different neuronal subtypes
.
Next, they evaluated the cellular and functional characteristics of the transformed glioma cells
.
It is worth noting that these transformed cells show an arrangement of intracellular organelles similar to neurons, and to a certain extent exhibit neuronal signal transmission activities
.
To verify their findings in vivo, the research team injected retroviruses expressing the above factors into the brains of mice transplanted with GBM cells
.
The results showed that GBM cells effectively transformed into mouse neuronal cells, as evidenced by the expression of neuronal biomarkers
.
In addition, cell transformation also significantly inhibited the proliferation of these cancer cells in animals
.
Together, these findings indicate that the reprogramming of glioma cells into neuron-type cells provides a promising therapeutic strategy that can slow the growth of glioblastoma
.
This targeted approach can also help overcome the harmful side effects of conventional anti-cancer treatments on healthy brain cells
.
Original link: http:// Open for reprinting, welcome to forward to Moments and WeChat groups
