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▎Editor of WuXi AppTec's content team Placing human stem cells in a laboratory dish and applying specific growth-promoting nutrients can encourage them to spontaneously form a "mini human brain" with a 3D structure.
Although it looks like a globular cluster of cells to the naked eye, it contains neurons with synaptic connections and other cell types that make up the cerebral cortex.
Scientists therefore call it "human brain organoids.
"
In fact, organoids are becoming a powerful tool for studying brain development and diseases.
It is generally believed that these mini-human brains differentiated from stem cells reflect the development of the prenatal stage, which is the earliest and simplest stage of the human brain.
However, a recent study published in Nature Neuroscience, a sub-Journal of Nature, revealed that when grown in a petri dish for a long enough time-250 to 300 days later, the cells in the mini-human brain appear and regenerate in terms of genetic characteristics.
Some key characteristics of the same brain cells.
One of the co-corresponding authors of this study is Professor Sergiu Pasca, a neurobiologist at Stanford University.
His research team has been committed to using organoids to study brain development and diseases for nearly a decade.
This time, they collaborated with Professor Daniel Geschwind of the University of California, Los Angeles (UCLA) to analyze the changes in the long-term growth of these mini-human brains cultured in vitro.
"So far, no one has been cultivating and characterizing these organoids for such a long period of time.
" Professor Geschwind said.
▲Professor Sergiu Pasca and Professor Daniel Geschwind (picture source: Stanford University and UCLA official website), who co-led the research, regularly take out cells in human brain organoids and use RNA sequencing to check gene expression, that is, which genes are actively being produced protein.
When they compared the results with RNA databases from human brain cells of different ages, they found that when human brain organoids grow to about 9 months-the same length as the length of time that human embryos develop in the body, their gene expression patterns have changed.
, Close to the brain cells of the newborn fetus.
The methylation patterns of these cells, that is, the chemical tags that attach to DNA and affect gene activity, also correspond to the increasingly mature human brain cells.
The researchers also recorded other signals in organoids that indicate maturity and found more critical developmental changes.
For example, before and after birth, the NMDA receptors of some brain cells gradually change, and one subunit of the receptor complex becomes more and the other subunit becomes less, which is very important for transmitting signals between neurons.
The cells in organoids also showed changes in the composition of NMDA receptor subunits.
However, the researchers cautioned that these findings do not mean that the mini-human brain itself is equivalent to the brain after birth.
For example, they do not have key features such as blood vessels and immune cells, and the electrical activity of the cells is also inconsistent with the developed human brain.
In addition, these organoids will not receive sensory input like the real human brain.
However, "even under the unnatural conditions of a laboratory dish, it is surprising that the cells themselves know how to progress.
" Professor Pasca said.
Image source: 123RF researchers pointed out that the new discovery will expand the scope of application of organoids and help us to better study brain diseases.
The huge application potential has attracted the attention of many scientists.
For example, in the opinion of Dr.
Madeline Lancaster, a developmental geneticist, she thought that using organoids to study schizophrenia might be difficult, because such diseases are generally believed to occur in the brain after birth, when neural communication has become complicated.
However, if the cells from patients can be "reprogrammed" to return to the original state of stem cells and mature in brain organoids, it may reveal important cell differences behind schizophrenia.
In fact, scientists also observed a series of genes related to brain diseases in this study, involving autism, schizophrenia, epilepsy and Alzheimer’s disease.
The research team determined that these genes are in brain organoids.
When did the expression activity in the brain rise and fall, as well as the correlation with the normal development time point of humans, so as to further guide how to use brain organoids to establish human disease models.
"Our research shows which aspects of human brain development can be modeled with high fidelity, which specific genes perform well in vitro, what is the best time to simulate disease, etc.
This is an important milestone.
" Professor Geschwind said .
Reference materials: [1] Gordon, A.
, et al.
Long-term maturation of human cortical organoids matches key early postnatal transitions.
Nat Neurosci (2021).
https://doi.
org/10.
1038/s41593-021-00802- y[2] Brain cell clusters, grown in lab for more than a year, mirror changes in a newborn's brain.
Retrieved Feb.
24, 2021 from https:// -clusters-grown-lab-more-year-mirror-changes-newborn-s-brain[3] Maturation of'mini brain' organoids matches human brain development Retrieved Feb.
24, from https:// pub_releases/2021-02/uoc--bo021821.
php
Although it looks like a globular cluster of cells to the naked eye, it contains neurons with synaptic connections and other cell types that make up the cerebral cortex.
Scientists therefore call it "human brain organoids.
"
In fact, organoids are becoming a powerful tool for studying brain development and diseases.
It is generally believed that these mini-human brains differentiated from stem cells reflect the development of the prenatal stage, which is the earliest and simplest stage of the human brain.
However, a recent study published in Nature Neuroscience, a sub-Journal of Nature, revealed that when grown in a petri dish for a long enough time-250 to 300 days later, the cells in the mini-human brain appear and regenerate in terms of genetic characteristics.
Some key characteristics of the same brain cells.
One of the co-corresponding authors of this study is Professor Sergiu Pasca, a neurobiologist at Stanford University.
His research team has been committed to using organoids to study brain development and diseases for nearly a decade.
This time, they collaborated with Professor Daniel Geschwind of the University of California, Los Angeles (UCLA) to analyze the changes in the long-term growth of these mini-human brains cultured in vitro.
"So far, no one has been cultivating and characterizing these organoids for such a long period of time.
" Professor Geschwind said.
▲Professor Sergiu Pasca and Professor Daniel Geschwind (picture source: Stanford University and UCLA official website), who co-led the research, regularly take out cells in human brain organoids and use RNA sequencing to check gene expression, that is, which genes are actively being produced protein.
When they compared the results with RNA databases from human brain cells of different ages, they found that when human brain organoids grow to about 9 months-the same length as the length of time that human embryos develop in the body, their gene expression patterns have changed.
, Close to the brain cells of the newborn fetus.
The methylation patterns of these cells, that is, the chemical tags that attach to DNA and affect gene activity, also correspond to the increasingly mature human brain cells.
The researchers also recorded other signals in organoids that indicate maturity and found more critical developmental changes.
For example, before and after birth, the NMDA receptors of some brain cells gradually change, and one subunit of the receptor complex becomes more and the other subunit becomes less, which is very important for transmitting signals between neurons.
The cells in organoids also showed changes in the composition of NMDA receptor subunits.
However, the researchers cautioned that these findings do not mean that the mini-human brain itself is equivalent to the brain after birth.
For example, they do not have key features such as blood vessels and immune cells, and the electrical activity of the cells is also inconsistent with the developed human brain.
In addition, these organoids will not receive sensory input like the real human brain.
However, "even under the unnatural conditions of a laboratory dish, it is surprising that the cells themselves know how to progress.
" Professor Pasca said.
Image source: 123RF researchers pointed out that the new discovery will expand the scope of application of organoids and help us to better study brain diseases.
The huge application potential has attracted the attention of many scientists.
For example, in the opinion of Dr.
Madeline Lancaster, a developmental geneticist, she thought that using organoids to study schizophrenia might be difficult, because such diseases are generally believed to occur in the brain after birth, when neural communication has become complicated.
However, if the cells from patients can be "reprogrammed" to return to the original state of stem cells and mature in brain organoids, it may reveal important cell differences behind schizophrenia.
In fact, scientists also observed a series of genes related to brain diseases in this study, involving autism, schizophrenia, epilepsy and Alzheimer’s disease.
The research team determined that these genes are in brain organoids.
When did the expression activity in the brain rise and fall, as well as the correlation with the normal development time point of humans, so as to further guide how to use brain organoids to establish human disease models.
"Our research shows which aspects of human brain development can be modeled with high fidelity, which specific genes perform well in vitro, what is the best time to simulate disease, etc.
This is an important milestone.
" Professor Geschwind said .
Reference materials: [1] Gordon, A.
, et al.
Long-term maturation of human cortical organoids matches key early postnatal transitions.
Nat Neurosci (2021).
https://doi.
org/10.
1038/s41593-021-00802- y[2] Brain cell clusters, grown in lab for more than a year, mirror changes in a newborn's brain.
Retrieved Feb.
24, 2021 from https:// -clusters-grown-lab-more-year-mirror-changes-newborn-s-brain[3] Maturation of'mini brain' organoids matches human brain development Retrieved Feb.
24, from https:// pub_releases/2021-02/uoc--bo021821.
php
