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Since the outbreak of the new type of coronavirus pneumonia (COVID-19), the number of people infected worldwide has exceeded 100 million, and the number of deaths has exceeded 2 million, which has brought great disasters to the global society and economy.
Understanding and understanding the pathogenesis of new coronary pneumonia is of great significance for diagnosis, treatment, prevention and control.
The wide application of single-cell transcriptome sequencing technology in various fields of life science has spawned many important biological discoveries.
However, the application of this technology in the study of new coronary pneumonia has high cost, small sample size, insufficient statistical power and reliable conclusions.
Sexual questions and other issues.
In order to quickly solve this problem, more than 40 hospitals, universities and research institutions in more than 10 provinces and cities in my country spontaneously formed the "Single Cell Consortium for COVID-19 in China ( SC4))”, which aims to coordinate the establishment of large data on the large cohort of single-cell transcriptomes of new coronary pneumonia, and make China's voice for revealing the pathogenesis and immunological characteristics of new coronary pneumonia.
After four and a half months of fighting day and night, the alliance obtained a total of 284 samples (including sputum, alveolar lavage fluid, pleural effusion, peripheral blood, etc.
) from 196 new crown patients (including normal controls).
Single cells with more than 25T and nearly 1.
5 million cells Transcriptome sequencing data, and data integration and analysis were quickly completed, revealing the mechanism of new coronavirus infection and the characteristics of the body's immune response at different stages of disease.
The research results were submitted to Cell magazine under the title "COVID-19 immune features revealed by a large-scale single cell transcriptome atlas" in September 2020, and published online on February 3, 2021.
This study found that in addition to the traditionally thought of respiratory epithelial cells, the nucleic acid sequence of the new coronavirus was detected in a variety of immune cells, including neutrophils, macrophages, plasma cells, T cells and natural killer cells.
Its expression characteristics also show subgenomic transcription characteristics, suggesting that the new coronavirus has experienced active transcription and replication in these immune cells, that is, it cannot be ruled out that the range of new coronavirus host cells includes not only epithelial cells but also immune cells.
This may be an important feature that distinguishes the new coronavirus from SARS, and it may also be the reason why the new coronavirus is highly infectious.
This finding is consistent with the strong interferon response of the new coronavirus nucleic acid-positive cells, and it was confirmed by staining the new coronavirus S protein in tissue sections.
Interestingly, the new crown receptor protein ACE2 is almost not expressed in immune cells, suggesting that the new crown virus may have potential new receptors to infect host cells.
Further bioinformatics analysis found that different epithelial cells will trigger different responses after the new coronavirus infection.
Viral nucleic acid positive and negative ciliated epithelial cells, secretory epithelial cells and squamous epithelial cells have different differential gene expressions.
New coronavirus-positive ciliated epithelial cells are more likely to fall off the tissue without causing an immune response; while the new coronavirus-positive squamous epithelial cells tend to enhance their interaction with neutrophils and macrophages, presumably using ANXA1-FPR1, S100A8/9-TLR4 ligand-receptor molecules trigger and initiate the body's immune response.
New coronavirus-positive squamous epithelial cells will up-regulate ANXA1, S100A8, S100A9, and interact with FPR1 and TLR4 that are highly expressed on neutrophils and macrophages, thereby triggering the body's natural immune response.
It is worth noting that ANXA1 and S100A8/9 will generally up-regulate expression in immune cells in the peripheral blood of critically ill patients during the onset of disease, suggesting that critically ill patients may have a systemic system mediated by ANXA1-FPR1, S100A8/9-TLR4 Immune response storm.
This study also lays the foundation for the analysis of the impact of the severity of new coronary pneumonia, the stage of disease, age, gender, and other technical factors on the composition of immune cells in the peripheral blood of the body.
Analysis of variance shows that severe patients with new coronary pneumonia have a higher proportion of proliferating plasma cells and T cells in the peripheral blood, and the overall T cell level is significantly lower than that of mild patients or healthy controls and convalescent patients.
There is a significant statistical correlation between these elevated proliferating plasma cells and T cells and the severity of the disease; while the overall B cells are more likely to be related to the disease stage, that is, there are higher B cell levels in the recovery period.
Epidemiological studies have revealed that age and gender are related to the symptoms of new crown patients.
This study found that age is mainly related to neutrophils and naive CD8+ T cells, and gender differences are mainly reflected in effector T cells.
Age and gender not only affect the level of different immune cell subgroups in peripheral blood, but also affect the diversity of B cell or T cell receptor spectrum.
Older patients have lower B cell or T cell spectrum diversity, and lower males, which may be related to the body's overall immunity.
Although cytokine storms are controversial in the pathogenic mechanism of new coronary pneumonia, this study provides detailed evidence for revealing the potential cellular sources of cytokines.
Among them, megakaryocytes and some subgroups of monocytes express high levels of various cytokines, and have higher expression levels in critically ill patients, and are potential sources of cytokine storms.
Plasma-based cytokine detection experiments confirmed the potential role of these cells in the cytokine storm.
Because some cytokines are secreted, these cytokines also constitute a bridge between the interaction of peripheral blood and lung infection lesions, forming a complex cytokine interaction network of the body.
Facing the major test of the new crown pneumonia, the single-cell sequencing alliance organized by Chinese scientists spontaneously organized the new crown pneumonia large cohort and single-cell big data in a short period of time, which provided new insights and new clues for revealing the pathogenesis and immune characteristics of the new crown pneumonia.
It is of great significance to prevent, control and treat new coronary pneumonia more effectively. The member units of the China New Coronary Pneumonia Single Cell Research Alliance include: Peking University, Naval Military Medical University, Guangzhou Biological Island Laboratory, Shenzhen Bay Laboratory, You'an Hospital Affiliated to Capital Medical University, University of Science and Technology of China, Shenzhen Third People's Hospital, Harbin University of Technology, Institute of Biophysics, Chinese Academy of Sciences, Sun Yat-sen University, Hospital of Hematology, Chinese Academy of Medical Sciences (Institute of Hematology), Army Military Medical University, Beijing Normal University, Baiao Zhihui Biotechnology Co.
, Ltd.
, Guangzhou No.
8 Affiliated to Guangzhou Medical University People's Hospital, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Biomedical Health, Chinese Academy of Sciences, Shanghai Public Health Clinical Center, Wuhan University People's Hospital, Huazhong University of Science and Technology, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, People of China The Fifth Medical Center of PLA General Hospital, Huanggang Hospital of Traditional Chinese Medicine, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shijitan Hospital Affiliated to Capital Medical University, Fudan University and other units.
10X Genomics and Baiao Zhihui provided strong support for this research.
The first authors of this article are: Ren Xianwen, Wenwen, Fan Xiaoying, Hou Wenhong, Su Bin, Cai Pengfei, Li Jiesheng, Liu Yang, Tang Fei, Zhang Fan, Yang Yu, He Jiangping, Ma Wenji, He Jingjing, Wang Pingping; the corresponding authors are: Zhou Penghui , Jiang Qinghua, Huang Zhiwei, Bei Jinxin, Wei Lai, Bian Xiuwu, Liu Xindong, Cheng Tao, Li Xiangpan, Zhao Pingsen, Wang Fusheng, Wang Hongyang, Su Bing, Zhang Zheng, Qu Kun, Wang Xiaoqun, Chen Jiekai, Jin Ronghua, Zhang Zemin (Lead Contact).
Original link: https:// Hot Article Selection in 2020 1.
Cups! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
"Feeling and rolling" for 28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight, and restored the old brain to a young state.
.
.
Understanding and understanding the pathogenesis of new coronary pneumonia is of great significance for diagnosis, treatment, prevention and control.
The wide application of single-cell transcriptome sequencing technology in various fields of life science has spawned many important biological discoveries.
However, the application of this technology in the study of new coronary pneumonia has high cost, small sample size, insufficient statistical power and reliable conclusions.
Sexual questions and other issues.
In order to quickly solve this problem, more than 40 hospitals, universities and research institutions in more than 10 provinces and cities in my country spontaneously formed the "Single Cell Consortium for COVID-19 in China ( SC4))”, which aims to coordinate the establishment of large data on the large cohort of single-cell transcriptomes of new coronary pneumonia, and make China's voice for revealing the pathogenesis and immunological characteristics of new coronary pneumonia.
After four and a half months of fighting day and night, the alliance obtained a total of 284 samples (including sputum, alveolar lavage fluid, pleural effusion, peripheral blood, etc.
) from 196 new crown patients (including normal controls).
Single cells with more than 25T and nearly 1.
5 million cells Transcriptome sequencing data, and data integration and analysis were quickly completed, revealing the mechanism of new coronavirus infection and the characteristics of the body's immune response at different stages of disease.
The research results were submitted to Cell magazine under the title "COVID-19 immune features revealed by a large-scale single cell transcriptome atlas" in September 2020, and published online on February 3, 2021.
This study found that in addition to the traditionally thought of respiratory epithelial cells, the nucleic acid sequence of the new coronavirus was detected in a variety of immune cells, including neutrophils, macrophages, plasma cells, T cells and natural killer cells.
Its expression characteristics also show subgenomic transcription characteristics, suggesting that the new coronavirus has experienced active transcription and replication in these immune cells, that is, it cannot be ruled out that the range of new coronavirus host cells includes not only epithelial cells but also immune cells.
This may be an important feature that distinguishes the new coronavirus from SARS, and it may also be the reason why the new coronavirus is highly infectious.
This finding is consistent with the strong interferon response of the new coronavirus nucleic acid-positive cells, and it was confirmed by staining the new coronavirus S protein in tissue sections.
Interestingly, the new crown receptor protein ACE2 is almost not expressed in immune cells, suggesting that the new crown virus may have potential new receptors to infect host cells.
Further bioinformatics analysis found that different epithelial cells will trigger different responses after the new coronavirus infection.
Viral nucleic acid positive and negative ciliated epithelial cells, secretory epithelial cells and squamous epithelial cells have different differential gene expressions.
New coronavirus-positive ciliated epithelial cells are more likely to fall off the tissue without causing an immune response; while the new coronavirus-positive squamous epithelial cells tend to enhance their interaction with neutrophils and macrophages, presumably using ANXA1-FPR1, S100A8/9-TLR4 ligand-receptor molecules trigger and initiate the body's immune response.
New coronavirus-positive squamous epithelial cells will up-regulate ANXA1, S100A8, S100A9, and interact with FPR1 and TLR4 that are highly expressed on neutrophils and macrophages, thereby triggering the body's natural immune response.
It is worth noting that ANXA1 and S100A8/9 will generally up-regulate expression in immune cells in the peripheral blood of critically ill patients during the onset of disease, suggesting that critically ill patients may have a systemic system mediated by ANXA1-FPR1, S100A8/9-TLR4 Immune response storm.
This study also lays the foundation for the analysis of the impact of the severity of new coronary pneumonia, the stage of disease, age, gender, and other technical factors on the composition of immune cells in the peripheral blood of the body.
Analysis of variance shows that severe patients with new coronary pneumonia have a higher proportion of proliferating plasma cells and T cells in the peripheral blood, and the overall T cell level is significantly lower than that of mild patients or healthy controls and convalescent patients.
There is a significant statistical correlation between these elevated proliferating plasma cells and T cells and the severity of the disease; while the overall B cells are more likely to be related to the disease stage, that is, there are higher B cell levels in the recovery period.
Epidemiological studies have revealed that age and gender are related to the symptoms of new crown patients.
This study found that age is mainly related to neutrophils and naive CD8+ T cells, and gender differences are mainly reflected in effector T cells.
Age and gender not only affect the level of different immune cell subgroups in peripheral blood, but also affect the diversity of B cell or T cell receptor spectrum.
Older patients have lower B cell or T cell spectrum diversity, and lower males, which may be related to the body's overall immunity.
Although cytokine storms are controversial in the pathogenic mechanism of new coronary pneumonia, this study provides detailed evidence for revealing the potential cellular sources of cytokines.
Among them, megakaryocytes and some subgroups of monocytes express high levels of various cytokines, and have higher expression levels in critically ill patients, and are potential sources of cytokine storms.
Plasma-based cytokine detection experiments confirmed the potential role of these cells in the cytokine storm.
Because some cytokines are secreted, these cytokines also constitute a bridge between the interaction of peripheral blood and lung infection lesions, forming a complex cytokine interaction network of the body.
Facing the major test of the new crown pneumonia, the single-cell sequencing alliance organized by Chinese scientists spontaneously organized the new crown pneumonia large cohort and single-cell big data in a short period of time, which provided new insights and new clues for revealing the pathogenesis and immune characteristics of the new crown pneumonia.
It is of great significance to prevent, control and treat new coronary pneumonia more effectively. The member units of the China New Coronary Pneumonia Single Cell Research Alliance include: Peking University, Naval Military Medical University, Guangzhou Biological Island Laboratory, Shenzhen Bay Laboratory, You'an Hospital Affiliated to Capital Medical University, University of Science and Technology of China, Shenzhen Third People's Hospital, Harbin University of Technology, Institute of Biophysics, Chinese Academy of Sciences, Sun Yat-sen University, Hospital of Hematology, Chinese Academy of Medical Sciences (Institute of Hematology), Army Military Medical University, Beijing Normal University, Baiao Zhihui Biotechnology Co.
, Ltd.
, Guangzhou No.
8 Affiliated to Guangzhou Medical University People's Hospital, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Biomedical Health, Chinese Academy of Sciences, Shanghai Public Health Clinical Center, Wuhan University People's Hospital, Huazhong University of Science and Technology, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, People of China The Fifth Medical Center of PLA General Hospital, Huanggang Hospital of Traditional Chinese Medicine, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shijitan Hospital Affiliated to Capital Medical University, Fudan University and other units.
10X Genomics and Baiao Zhihui provided strong support for this research.
The first authors of this article are: Ren Xianwen, Wenwen, Fan Xiaoying, Hou Wenhong, Su Bin, Cai Pengfei, Li Jiesheng, Liu Yang, Tang Fei, Zhang Fan, Yang Yu, He Jiangping, Ma Wenji, He Jingjing, Wang Pingping; the corresponding authors are: Zhou Penghui , Jiang Qinghua, Huang Zhiwei, Bei Jinxin, Wei Lai, Bian Xiuwu, Liu Xindong, Cheng Tao, Li Xiangpan, Zhao Pingsen, Wang Fusheng, Wang Hongyang, Su Bing, Zhang Zheng, Qu Kun, Wang Xiaoqun, Chen Jiekai, Jin Ronghua, Zhang Zemin (Lead Contact).
Original link: https:// Hot Article Selection in 2020 1.
Cups! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
"Feeling and rolling" for 28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight, and restored the old brain to a young state.
.
.
