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Written by | Li Humans can express their emotions in various languages and even mood particles.
For example, "Aiyo~Aiyo~Aiyo" is likely to be unbearable in pain
.
There are many reasons for pain, but it can be considered as some kind of injury, which is sensed by the body's nociceptor, and then transmits this "dangerous" signal to our central nervous system.
so that we can react in various ways
.
Anatomically, nociceptors are the peripheral parts of primary sensory neurons in the dorsal root ganglia and trigeminal ganglia that sense and transmit nociceptive signals and are widely found in the skin, muscles, Internal organs, etc.
From a cellular point of view, nociceptors are the "sentinels" of pain pathways and can express various receptors to sense various stimuli from the external environment and even local cells (such as infiltrating immune cells)
.
Precisely because nociceptors are one of the most important links in perceiving and transmitting pain, they are also the most important targets for the treatment of various pains clinically
.
In the process of drug development, including painkillers, animal models are often used for preclinical testing, but unfortunately, although the pain mechanism of these animals (such as rodents and mice) is well studied, the mechanism The translation into clinical outcomes is unsatisfactory
.
The reason is that there are differences in the molecular phenotype of nociceptors in mice and humans, and this view has also been confirmed by many studies.
Therefore, it is urgent to characterize the molecular characteristics of human nociceptors in detail
.
On February 16, 2022, the team of Theodore J.
Price of the University of Texas at Dallas published an article in Science Translational Medicine Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors, using 10x Genomics Visium spatial transcriptome technology to analyze eight Single-cell resolution spatial transcriptome analysis of the dorsal root ganglia of donor organs identified 12 clusters of sensory neurons
.
First, the researchers selected 4 male and 4 female (dead) donors, and the dorsal root ganglia were removed and sectioned, placed on Visium slides, stained, and imaged
.
After that, the tissue of each region was permeabilized, and the mRNA was ligated with barcode primers for library construction and sequencing
.
On average, each section has about 52M reads and 24,000 gene expressions, and all 16 sections have a total of about 830M reads
.
Figure: Experimental flow chart Next, the researchers identified 12 clusters of human dorsal root neurons (c.
01-c.
12, below) by enrichment analysis of gene signatures and integration of sets
.
According to diameter and conduction velocity, nerves can be divided into A fibers and C fibers
.
In A fibers, the researchers identified 6 subtypes, including c.
01, c02, c03, c04, c05, c07; in C fibers, identified 5 subtypes c06, c08, c09, c10, c11; There is 1 putative C-LTMR (c.
12)
.
Each cluster of neurons has its own unique expression characteristics
.
Since the above analysis did not incorporate spatial information, the researchers used DRG slice barcode visualization to supplement the spatial information, and used RNAscope experiments to verify the identified neural clusters
.
Because the donors were gendered, the researchers also found gender differences in neurons, such as higher expression of the CGRP protein in female neurons than in males
.
In addition to gender differences, the researchers finally compared the similarities and differences between human and mouse, and non-human primate (rhesus monkey) neurons
.
In conclusion, this study utilizes 10x Genomics' Visium spatial transcriptome technology to present a single-neuron-resolution cellularity and molecular phenotype map of DRGs, as well as molecular characterization of different species and different sexes of the same species.
The comparison partly explains why the efficacy of the same drug is different in different species, and also lays the foundation for better development of pain relief drugs in the future
.
Link to the original text: https://doi.
org/10.
1126/scitranslmed.
abj8186 Publisher: 11th Reprint Instructions [Original article] BioArt original article, welcome to forward and share it, reprinting is prohibited without permission, and the copyright of all works published is Owned by BioArt
.
BioArt reserves all legal rights and violators will be held accountable
.
Click to read the original text for the "Visium Spatial Analysis and Experiment Planning Resources" information
.
For example, "Aiyo~Aiyo~Aiyo" is likely to be unbearable in pain
.
There are many reasons for pain, but it can be considered as some kind of injury, which is sensed by the body's nociceptor, and then transmits this "dangerous" signal to our central nervous system.
so that we can react in various ways
.
Anatomically, nociceptors are the peripheral parts of primary sensory neurons in the dorsal root ganglia and trigeminal ganglia that sense and transmit nociceptive signals and are widely found in the skin, muscles, Internal organs, etc.
From a cellular point of view, nociceptors are the "sentinels" of pain pathways and can express various receptors to sense various stimuli from the external environment and even local cells (such as infiltrating immune cells)
.
Precisely because nociceptors are one of the most important links in perceiving and transmitting pain, they are also the most important targets for the treatment of various pains clinically
.
In the process of drug development, including painkillers, animal models are often used for preclinical testing, but unfortunately, although the pain mechanism of these animals (such as rodents and mice) is well studied, the mechanism The translation into clinical outcomes is unsatisfactory
.
The reason is that there are differences in the molecular phenotype of nociceptors in mice and humans, and this view has also been confirmed by many studies.
Therefore, it is urgent to characterize the molecular characteristics of human nociceptors in detail
.
On February 16, 2022, the team of Theodore J.
Price of the University of Texas at Dallas published an article in Science Translational Medicine Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors, using 10x Genomics Visium spatial transcriptome technology to analyze eight Single-cell resolution spatial transcriptome analysis of the dorsal root ganglia of donor organs identified 12 clusters of sensory neurons
.
First, the researchers selected 4 male and 4 female (dead) donors, and the dorsal root ganglia were removed and sectioned, placed on Visium slides, stained, and imaged
.
After that, the tissue of each region was permeabilized, and the mRNA was ligated with barcode primers for library construction and sequencing
.
On average, each section has about 52M reads and 24,000 gene expressions, and all 16 sections have a total of about 830M reads
.
Figure: Experimental flow chart Next, the researchers identified 12 clusters of human dorsal root neurons (c.
01-c.
12, below) by enrichment analysis of gene signatures and integration of sets
.
According to diameter and conduction velocity, nerves can be divided into A fibers and C fibers
.
In A fibers, the researchers identified 6 subtypes, including c.
01, c02, c03, c04, c05, c07; in C fibers, identified 5 subtypes c06, c08, c09, c10, c11; There is 1 putative C-LTMR (c.
12)
.
Each cluster of neurons has its own unique expression characteristics
.
Since the above analysis did not incorporate spatial information, the researchers used DRG slice barcode visualization to supplement the spatial information, and used RNAscope experiments to verify the identified neural clusters
.
Because the donors were gendered, the researchers also found gender differences in neurons, such as higher expression of the CGRP protein in female neurons than in males
.
In addition to gender differences, the researchers finally compared the similarities and differences between human and mouse, and non-human primate (rhesus monkey) neurons
.
In conclusion, this study utilizes 10x Genomics' Visium spatial transcriptome technology to present a single-neuron-resolution cellularity and molecular phenotype map of DRGs, as well as molecular characterization of different species and different sexes of the same species.
The comparison partly explains why the efficacy of the same drug is different in different species, and also lays the foundation for better development of pain relief drugs in the future
.
Link to the original text: https://doi.
org/10.
1126/scitranslmed.
abj8186 Publisher: 11th Reprint Instructions [Original article] BioArt original article, welcome to forward and share it, reprinting is prohibited without permission, and the copyright of all works published is Owned by BioArt
.
BioArt reserves all legal rights and violators will be held accountable
.
Click to read the original text for the "Visium Spatial Analysis and Experiment Planning Resources" information
.
