"This is the first comprehensive study of brain development to focus on gene regulation. Previous studies have almost always focused on the cerebral cortex. Our study is a systematic mapping of the whole brain so that all regions can be compared to each other." Said Sten Linnarsson, professor of molecular systems biology at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, who led the study.
One of the most exciting findings of the new study was the identification of 135 distinct cell populations, each representing a unique cell type or state. These cell populations include various types of neurons as well as support cells such as glial cells. By comparing the genetic characteristics of these cell populations, the researchers were able to trace the developmental trajectory that led to brain diversity.
Of the neurons in the brain, Purkinje neurons are the largest and are the "master motor coordinators." The researchers found that Purkinje neurons play a crucial role in motor and balance coordination and follow a specific developmental path. This pathway is guided by a series of gene activation and silencing sequences precisely regulated by the brain and driven by special proteins called transcription factors.
To better understand how transcription factors work, Swedish researchers used convolutional neural networks (CNNS), an artificial intelligence tool, to help them identify specific DNA sequences to which transcription factors bind.
Transcription factors are a class of proteins that can regulate gene expression, and when transcription factors bind to specific DNA sequences, they can control gene activity like a molecular switch,
that is, turning gene expression on or off. Therefore, by identifying the DNA sequences to which these transcription factors bind, researchers can better understand the mechanisms of gene regulation, that is, which genes are turned on or off, which in turn affect the function and properties of cells.
Using CNN, the researchers were able to decipher the regulatory language that controls the development of Purkinje neurons. They found that a transcription factor called ESRRB plays a central role in regulating Purkinje neuron development,
and activation of ESRRB requires two processes that involve other transcription factors such as TFAP2B and LHX5. This intricate process of gene regulation ensures the normal development of Purkinje neurons and takes up a place in the complex circuits of the cerebellum.
To help understand brain-related diseases
In addition to providing fundamental insights into brain development, this research has important implications for understanding neurodevelopmental disorders. Many disorders, such as autism and schizophrenia,
are thought to originate in the early stages of brain formation. The researchers also found that GABAergic interneurons may be particularly vulnerable to genetic mutations associated with major depression.
In addition, the newly mapped early brain development could also help identify problems in the development of childhood brain tumors and provide clues for finding new treatments.
Liu Shiping said that childhood brain tumors usually refer to primary brain tumors, that is, tumors originating in the brain or its nearby tissues. Primary brain tumors occur when a mutation occurs in the DNA of a normal cell.
These mutations allow normal cells to grow and divide at a faster rate, and keep healthy cells alive when they should die, which creates a large number of abnormal cells that can form tumors. About 7,000 children in China are diagnosed with brain tumors every year.
"We are studying primary brain tumors that occur during fetal brain development and trying to use the new genetic map to understand why normal developmental processes become abnormal and how these abnormalities drive tumor formation and growth," Lineson said.
Liu Shiping believes that previous studies have revealed that specific stem cell types and epigenetic regulators are crucial for the occurrence and development of childhood brain tumors.
This study identified detailed cell types and key epigenetic regulatory factors in various brain regions in the early and middle stages of brain development, laying a theoretical foundation for the study of the origin and pathogenesis of childhood brain tumors, and also providing data resources for the screening of disease targets.Pan Jianwei was elected a foreign Fellow of the Royal SocietyPan Jianwei, a professor at the University of Science and Technology of China, has been elected as a foreign member of the Royal Society, the only Chinese scientist elected as a foreign member of the Royal Society, the Royal Society announced on May 16.
Sir Adrian Smith, President of the Royal Society, commented: "This new group of members has already made a significant contribution to our understanding of the world and continues to push the boundaries of what is possible in academic research and industry."
Pan Jianwei is mainly engaged in experimental research in quantum optics, quantum information and the testing of fundamental problems in quantum mechanics, and the Royal Society commented on his election:
"Pan Jianwei's pioneering contributions have turned the advantages of secure quantum communication and quantum computing from a dream to a reality on a global scale." Through the "Micius" quantum satellite, Pan Jianwei achieved the first intercontinental quantum encrypted video conference,
which opened the grand prospect of quantum Internet from the ground to space. Based on multiparticle interferometry, he has built quantum computing systems that can outperform classical computers in solving specific problems."
