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The development of the human brain is a complex process, including the proliferation, differentiation, migration, maturation of nerve cells and the establishment of neural networks.
At different stages of brain development, it is regulated by a variety of different key genes.
Abnormal functions of these key genes can lead to a variety of neurological diseases such as giant gyrus, microcephaly, and autism.
However, many important transcription factors and signal proteins (such as protein kinases) may not have DNA mutations or differences in mRNA or protein expression levels, but they may be through protein synthesis and degradation, post-translational modification, complex formation or subcellular localization, etc.
The process has a huge impact on the expression of its downstream regulated target gene (that is, the activity of the gene), which is difficult to identify by traditional methods (such genes are called hidden drivers).
On March 2, 2021, Zhou Wenhao/Xiong Man’s research team from the Pediatric Hospital of Fudan University published a paper Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment on Cell Reports.
Team members Dr.
Xinran Dong and The United States Jiyang Yu Lab cooperated to develop the NetBID algorithm (https://github.
com/jyyulab/NetBID/).
Using this algorithm, team members analyzed the human brain RNAseq data at different stages of development in the Brainspan database, and successfully found the hidden driver SYTL3 that regulates early human brain development (the gene expression changes little, but the gene activity is the highest).
To verify this phenomenon, team members directed differentiation of human embryonic stem cells into neural cells (neural precursor cells, terminal neurons) in different developmental stages in vitro and performed RNASeq sequencing.
They found that SYTL3 had the lowest expression level at the neuronal stage, but The activity of its genes rose significantly at this stage; knocking out the SYTL3 gene significantly affected the gene expression network of neurons, but had little effect on the expression of genes in other developmental stages (embryonic stem cells, neural precursor cells).
This result further proves that SYTL3 acts as a hidden driver to regulate genes in the process of neurodevelopment.
The results of functional tests found that SYTL3 gene knockout not only affects the distribution of cortical neural precursor cells of the brain-like organs differentiated from the embryonic stem cell line and the release of neurotransmitters from the differentiated terminal neurons, but also up-regulates the matrix metalloproteinase (MMP).
, MMP) expression regulates the remodeling of extracellular matrix to promote neuronal migration (Figure 2).
Through the NetBID series of bioinformatics algorithms, it is possible to find hidden driving factors that are not abnormal in DNA/RNA expression, but play an important role in brain development or disease occurrence.
In addition, the directional differentiation of neurons/human-like brain organs of human embryonic stem cell lines can well mimic the process of brain development.
This method combined with gene editing can conduct in-depth research on the important role of genes in development or disease pathogenesis.
At present, the Molecular Medicine Center of Pediatrics Hospital of Fudan University has completed clinical molecular diagnosis of nearly 50,000 cases of rare childhood diseases.
Only about 30% of the causes of brain developmental diseases can be identified through gene sequencing, and there are still about 70% of patients.
Unable to find the cause.
The experimental verification of inducible pluripotent stem cells from human embryonic stem cells/patients through the development of bioinformatics algorithms provides new ideas and methods for finding the pathogenesis of diseases and potential therapeutic targets.
Researcher Xiong Man from the Institute of Pediatrics, Pediatric Hospital of Fudan University, has been engaged in developmental encephalopathy and stem cell therapy for brain injury since he returned to China in 2016.
He has published many authoritative papers in related fields as the first author or corresponding author.
His stem cell center will Recruit an electrophysiological technician. Resume delivery (please send your resume to): https://jinshuju.
net/f/ZqXwZt or scan the QR code to deliver the original resume link: https://doi.
org/10.
1016/j.
celrep.
2021.
108802 The copyright of this article belongs to the author of the article.
Reprinting is prohibited without permission.
The author has all legal rights and offenders must be investigated.
Plate maker: Eleven
At different stages of brain development, it is regulated by a variety of different key genes.
Abnormal functions of these key genes can lead to a variety of neurological diseases such as giant gyrus, microcephaly, and autism.
However, many important transcription factors and signal proteins (such as protein kinases) may not have DNA mutations or differences in mRNA or protein expression levels, but they may be through protein synthesis and degradation, post-translational modification, complex formation or subcellular localization, etc.
The process has a huge impact on the expression of its downstream regulated target gene (that is, the activity of the gene), which is difficult to identify by traditional methods (such genes are called hidden drivers).
On March 2, 2021, Zhou Wenhao/Xiong Man’s research team from the Pediatric Hospital of Fudan University published a paper Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment on Cell Reports.
Team members Dr.
Xinran Dong and The United States Jiyang Yu Lab cooperated to develop the NetBID algorithm (https://github.
com/jyyulab/NetBID/).
Using this algorithm, team members analyzed the human brain RNAseq data at different stages of development in the Brainspan database, and successfully found the hidden driver SYTL3 that regulates early human brain development (the gene expression changes little, but the gene activity is the highest).
To verify this phenomenon, team members directed differentiation of human embryonic stem cells into neural cells (neural precursor cells, terminal neurons) in different developmental stages in vitro and performed RNASeq sequencing.
They found that SYTL3 had the lowest expression level at the neuronal stage, but The activity of its genes rose significantly at this stage; knocking out the SYTL3 gene significantly affected the gene expression network of neurons, but had little effect on the expression of genes in other developmental stages (embryonic stem cells, neural precursor cells).
This result further proves that SYTL3 acts as a hidden driver to regulate genes in the process of neurodevelopment.
The results of functional tests found that SYTL3 gene knockout not only affects the distribution of cortical neural precursor cells of the brain-like organs differentiated from the embryonic stem cell line and the release of neurotransmitters from the differentiated terminal neurons, but also up-regulates the matrix metalloproteinase (MMP).
, MMP) expression regulates the remodeling of extracellular matrix to promote neuronal migration (Figure 2).
Through the NetBID series of bioinformatics algorithms, it is possible to find hidden driving factors that are not abnormal in DNA/RNA expression, but play an important role in brain development or disease occurrence.
In addition, the directional differentiation of neurons/human-like brain organs of human embryonic stem cell lines can well mimic the process of brain development.
This method combined with gene editing can conduct in-depth research on the important role of genes in development or disease pathogenesis.
At present, the Molecular Medicine Center of Pediatrics Hospital of Fudan University has completed clinical molecular diagnosis of nearly 50,000 cases of rare childhood diseases.
Only about 30% of the causes of brain developmental diseases can be identified through gene sequencing, and there are still about 70% of patients.
Unable to find the cause.
The experimental verification of inducible pluripotent stem cells from human embryonic stem cells/patients through the development of bioinformatics algorithms provides new ideas and methods for finding the pathogenesis of diseases and potential therapeutic targets.
Researcher Xiong Man from the Institute of Pediatrics, Pediatric Hospital of Fudan University, has been engaged in developmental encephalopathy and stem cell therapy for brain injury since he returned to China in 2016.
He has published many authoritative papers in related fields as the first author or corresponding author.
His stem cell center will Recruit an electrophysiological technician. Resume delivery (please send your resume to): https://jinshuju.
net/f/ZqXwZt or scan the QR code to deliver the original resume link: https://doi.
org/10.
1016/j.
celrep.
2021.
108802 The copyright of this article belongs to the author of the article.
Reprinting is prohibited without permission.
The author has all legal rights and offenders must be investigated.
Plate maker: Eleven
