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Written by NAN | XI The adult neurogenesis of the hippocampus is a biological process ubiquitous in mammals (except cetaceans)
.
However, whether this process exists in the adult brain is a topic that has been debated for decades in the field of neuroscience (Cell Stem Cell focuses on the controversy | In old age or disease, the human brain still has nerve regeneration in the hippocampus).
Some studies give There is evidence to support the existence of this process, but other studies have confirmed that the process has been reduced sharply after adulthood, and it is almost impossible to detect (experts question Nat Med | 90 years old, there is still nerve regeneration in the brain? Nerve regeneration has staged a "fairy" Fight")
.
The reason why this research direction is controversial is that mouse-related experiments show that this process may be related to intelligence, memory and learning.
At the same time, this process is also expected to treat a variety of mental diseases, such as Alzheimer's disease [1]
.
In summary, there is an urgent need for a new method to resolve this dispute and to reconcile the conflicting results of different studies
.
As a popular technique in recent years, single-cell transcriptome analysis has been applied to the hippocampus of adult mice in an article published in 2018 to study adult neurogenesis [2]
.
Through cluster analysis, the researchers discovered a series of key cell types from neural stem cells to mature granule cells in the cell differentiation process of mouse hippocampal granule cells
.
This result proves that single-cell transcriptome analysis, as a powerful method, is expected to solve the mystery that has plagued the field of neuroscience for many years
.
On November 18, 2021, the Nenad Sestan research group of Yale University in the United States published an article titled: Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells in Neuron
.
Through the single-cell transcriptome integration analysis of the hippocampus of human, rhesus macaque and pigs, they found very obvious cell differentiation trajectories of hippocampal granulosa cells in the hippocampus of rhesus macaques and pigs (from neural stem cells).
To mature granular cells), but the trajectory does not exist in the human brain, further proving that the process of new neuron generation in the adult brain does not exist or is very rare
.
In this study, the researchers used the hippocampal single-cell transcriptome data of adult mice in 2018, and then achieved data integration analysis of cell transcriptome across four species (human, monkey, pig, and mouse)
.
Among them, the mouse is a very complete model for studying adult neuron generation, and the monkey is a representative of non-human primates.
Although its adult neuron generation level is much lower than that of mice, it can also be clearly detected
.
The pig species is used as a model to control the time interval after brain death in this article.
If you are interested, you can click on the original text for more details
.
The cross-species integration analysis showed that homologous cells from different species were clustered together, such as mature granular cells shared by four species
.
Interestingly, in the brains of mice, pigs, and monkeys, nIPC (neural intermediate progenitor cells) and neuroblast (neuroblasts) that produce mature granule cells are clustered together and connected to mature granule cells to form The trajectory of differentiation from stem cells to mature granular cells
.
Although the amount of data in humans is 25 times that of mice, only one nIPC-like and one neuroblast-like cell were found in the human hippocampus
.
If calculated according to various previous studies that support neurogenesis in the adult brain [3, 4], there should be 28 to 1218 neuroblast cells in a considerable amount of human brain data.
It can be seen that the generation of human adult neurons is very rare or even uncommon.
Does not exist
.
Previous studies supporting adult neuron generation are mainly divided into two parts.
One part is the detection of cell proliferation, which represents the integration of C14 isotope into human brain DNA caused by atomic energy experiments [3], and the study of artificial injection of BrdU into DNA [5] 】
.
But these studies cannot be repeated, because such experiments cannot be performed directly on humans
.
The other part is the more commonly used immunostaining experiment, represented by the protein immunostaining of the neuroblast marker DCX [4]
.
The research team then further studied the cross-species DCX gene expression profile and found that DCX does not label Neuroblast in the human brain, but instead mainly labels mature neurons, especially interneurons
.
Through DCX immunostaining, they found that DCX protein can well label neuroblast cells in mice, pigs and rhesus monkeys, but there are only sporadic very low signals in the human brain
.
And many of these low-signal human brain cells also express interneuron markers, which further proves that the neurogenesis process does not exist in the adult brain, and suggests that the cells found by DCX immunostaining are likely to be mature neurons, such as interneurons.
Neuron
.
Another key finding of the study is that they further studied the published single-cell transcriptome data of the adult hippocampus, including a study published in Neuron by Genevieve Konopka's laboratory in 2021 [6], claiming to have discovered a neural stem cell cell Type
.
However, further research found that each cell of the cell population is actually a mixed cell (doublets) including granular cells and oligodendrocytes
.
In summary, the study through cross-species single-cell data integration analysis, immunostaining analysis, and re-analysis of published data proves that neurogenesis in the adult brain is very rare or even non-existent, and it reconciles the observations of previous immunostaining studies.
The seemingly conflicting results indicate that the previously observed cells may be mature neurons rather than neuroblast cells
.
Original link: https://doi.
org/10.
1016/j.
neuron.
2021.
10.
036 Platemaker: 11 References 1.
A.
Duque, JI Arellano, P.
Rakic, An assessment of the existence of adult neurogenesis in humans and value of its rodent models for neuropsychiatric diseases.
Mol Psychiatry, (2021).
2.
H.
Hochgerner, A.
Zeisel, P.
Lonnerberg, S.
Linnarsson, Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing.
Nat Neurosci 21, 290-299 (2018) 3.
KL Spalding et al.
, Dynamics of hippocampal neurogenesis in adult humans.
Cell 153, 1219-1227 (2013).
4.
EP Moreno-Jimenez et al.
, Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease.
Nat Med 25, 554-560 (2019).
5.
PS Eriksson et al.
, Neurogenesis in the adult human hippocampus.
Nat Med 4,1313-1317 (1998).
6.
F.
Ayhan et al.
, Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans.
Neuron 109, 2091-2105 e2096 (2021).
Reprinting instructions【Original article】 BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt. .
BioArt reserves all statutory rights and offenders must be investigated
.
.
However, whether this process exists in the adult brain is a topic that has been debated for decades in the field of neuroscience (Cell Stem Cell focuses on the controversy | In old age or disease, the human brain still has nerve regeneration in the hippocampus).
Some studies give There is evidence to support the existence of this process, but other studies have confirmed that the process has been reduced sharply after adulthood, and it is almost impossible to detect (experts question Nat Med | 90 years old, there is still nerve regeneration in the brain? Nerve regeneration has staged a "fairy" Fight")
.
The reason why this research direction is controversial is that mouse-related experiments show that this process may be related to intelligence, memory and learning.
At the same time, this process is also expected to treat a variety of mental diseases, such as Alzheimer's disease [1]
.
In summary, there is an urgent need for a new method to resolve this dispute and to reconcile the conflicting results of different studies
.
As a popular technique in recent years, single-cell transcriptome analysis has been applied to the hippocampus of adult mice in an article published in 2018 to study adult neurogenesis [2]
.
Through cluster analysis, the researchers discovered a series of key cell types from neural stem cells to mature granule cells in the cell differentiation process of mouse hippocampal granule cells
.
This result proves that single-cell transcriptome analysis, as a powerful method, is expected to solve the mystery that has plagued the field of neuroscience for many years
.
On November 18, 2021, the Nenad Sestan research group of Yale University in the United States published an article titled: Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells in Neuron
.
Through the single-cell transcriptome integration analysis of the hippocampus of human, rhesus macaque and pigs, they found very obvious cell differentiation trajectories of hippocampal granulosa cells in the hippocampus of rhesus macaques and pigs (from neural stem cells).
To mature granular cells), but the trajectory does not exist in the human brain, further proving that the process of new neuron generation in the adult brain does not exist or is very rare
.
In this study, the researchers used the hippocampal single-cell transcriptome data of adult mice in 2018, and then achieved data integration analysis of cell transcriptome across four species (human, monkey, pig, and mouse)
.
Among them, the mouse is a very complete model for studying adult neuron generation, and the monkey is a representative of non-human primates.
Although its adult neuron generation level is much lower than that of mice, it can also be clearly detected
.
The pig species is used as a model to control the time interval after brain death in this article.
If you are interested, you can click on the original text for more details
.
The cross-species integration analysis showed that homologous cells from different species were clustered together, such as mature granular cells shared by four species
.
Interestingly, in the brains of mice, pigs, and monkeys, nIPC (neural intermediate progenitor cells) and neuroblast (neuroblasts) that produce mature granule cells are clustered together and connected to mature granule cells to form The trajectory of differentiation from stem cells to mature granular cells
.
Although the amount of data in humans is 25 times that of mice, only one nIPC-like and one neuroblast-like cell were found in the human hippocampus
.
If calculated according to various previous studies that support neurogenesis in the adult brain [3, 4], there should be 28 to 1218 neuroblast cells in a considerable amount of human brain data.
It can be seen that the generation of human adult neurons is very rare or even uncommon.
Does not exist
.
Previous studies supporting adult neuron generation are mainly divided into two parts.
One part is the detection of cell proliferation, which represents the integration of C14 isotope into human brain DNA caused by atomic energy experiments [3], and the study of artificial injection of BrdU into DNA [5] 】
.
But these studies cannot be repeated, because such experiments cannot be performed directly on humans
.
The other part is the more commonly used immunostaining experiment, represented by the protein immunostaining of the neuroblast marker DCX [4]
.
The research team then further studied the cross-species DCX gene expression profile and found that DCX does not label Neuroblast in the human brain, but instead mainly labels mature neurons, especially interneurons
.
Through DCX immunostaining, they found that DCX protein can well label neuroblast cells in mice, pigs and rhesus monkeys, but there are only sporadic very low signals in the human brain
.
And many of these low-signal human brain cells also express interneuron markers, which further proves that the neurogenesis process does not exist in the adult brain, and suggests that the cells found by DCX immunostaining are likely to be mature neurons, such as interneurons.
Neuron
.
Another key finding of the study is that they further studied the published single-cell transcriptome data of the adult hippocampus, including a study published in Neuron by Genevieve Konopka's laboratory in 2021 [6], claiming to have discovered a neural stem cell cell Type
.
However, further research found that each cell of the cell population is actually a mixed cell (doublets) including granular cells and oligodendrocytes
.
In summary, the study through cross-species single-cell data integration analysis, immunostaining analysis, and re-analysis of published data proves that neurogenesis in the adult brain is very rare or even non-existent, and it reconciles the observations of previous immunostaining studies.
The seemingly conflicting results indicate that the previously observed cells may be mature neurons rather than neuroblast cells
.
Original link: https://doi.
org/10.
1016/j.
neuron.
2021.
10.
036 Platemaker: 11 References 1.
A.
Duque, JI Arellano, P.
Rakic, An assessment of the existence of adult neurogenesis in humans and value of its rodent models for neuropsychiatric diseases.
Mol Psychiatry, (2021).
2.
H.
Hochgerner, A.
Zeisel, P.
Lonnerberg, S.
Linnarsson, Conserved properties of dentate gyrus neurogenesis across postnatal development revealed by single-cell RNA sequencing.
Nat Neurosci 21, 290-299 (2018) 3.
KL Spalding et al.
, Dynamics of hippocampal neurogenesis in adult humans.
Cell 153, 1219-1227 (2013).
4.
EP Moreno-Jimenez et al.
, Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease.
Nat Med 25, 554-560 (2019).
5.
PS Eriksson et al.
, Neurogenesis in the adult human hippocampus.
Nat Med 4,1313-1317 (1998).
6.
F.
Ayhan et al.
, Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans.
Neuron 109, 2091-2105 e2096 (2021).
Reprinting instructions【Original article】 BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt. .
BioArt reserves all statutory rights and offenders must be investigated
.
