cell map plays an important role in elucidating the mechanism of action of various tissues and organs in mammals including humans. An in-depth understanding of the cell atlas of these tissues and organs in health and disease will help to develop new therapies. In view of the latest developments in cell atlases, the editor will sort out for readers.
1. Nature: Constructed a cellular map of the human lung, laying the foundation for understanding and curing lung diseases In a new study, researchers from Stanford University in the United States constructed a cell map of the human lung, which highlights dozens of cell types that make up different parts of the lung. The relevant research results were published online in Nature on November 18, 2020, and the title of the paper is "A molecular cell atlas of the human lung from single-cell RNA sequencing". In this paper, they described their research work (mainly involving single cell RNA sequencing) and some things they learned about the lungs during the research work. 
The picture comes from CC0 Public Domain.
In order to construct an atlas of lung cells,The researchers collected tissue samples from the bronchioles, bronchi, and alveolar areas of the lungs, as well as related blood samples. Each sample is broken down into its cellular components and then classified by type: immune cells , epithelial cells, endothelial cells or stromal cells.
These researchers generated transcriptomes for approximately 75,000 cells. Using the markers, they then performed a cluster analysis of these cells, revealing 58 different cell populations. In doing so, they were able to generate an expression profile of 91% of lung cell types, and they also discovered 14 lung cell types previously unknown to science. They also discovered about 200 markers that can be used to identify the unknown lung cell types they found.
2. Two Science papers constructed a human cell map of fetal gene expression and chromatin accessibility, which will help reveal the mechanism of human cell growth and development
strong7:10.1span doi science.aba7721; doi:10.1126/science.aba7612
In two new studies, researchers from the United States , Washington University School of Medicine and Brotman-Batti Institute for Precision Medicine Two cell maps were constructed to track gene expression during human cell types and tissue development and chromatin accessibility (chromatin accessibility, also translated as chromatin accessibility). One of the cell maps maps the gene expression in individual cells in 15 fetal tissues, and the other cell map maps the chromatin accessibility of individual cells in these cells.Related research results were published in two Science papers on November 13, 2020, with the titles of "A human cell atlas of fetal gene expression" and "A human cell atlas of fetal chromatin accessibility".
These maps together provide an unprecedented scale of basic resources for understanding gene expression and chromatin accessibility during human development. In addition, the techniques described in these two papers make it possible to generate gene expression and chromatin accessibility data for millions of cells.
In the first study, in order to create a gene expression profile, these researchers used a technology called sci-RNA-seq3 to analyze the gene expression of 15 fetal tissues. This technology attaches a unique combination of three DNA barcodes to each cell, allowing them to track these cells without physically separating them.
After these DNA barcode sequences were obtained, they used computer algorithms to obtain single-cell information, clustered the cells by cell type and subtype, and determined their developmental trajectories. They analyzed more than 4 million single cells and identified 77 main cell types and approximately 650 cell subtypes.
In the second study, in order to analyze the accessibility of DNA in a single cell, these researchers developed a new method called sci-ATAC-seq3. Like sci-RNA-seq3, this technology uses three different DNA "barcodes" in each cell to label and track individual cells. However, sci-ATAC-seq3 does not recognize all currently expressed sequences, but instead captures open chromatin sites and performs sequencing.
In this new study, these researchers generated nearly 800,000 single-cell chromatin accessibility data at approximately 1 million sites in 15 fetal tissues.They studied which proteins might interact with accessible DNA sites in each cell, and how these interactions explain the cell type. This analysis identified developmental control switches within the genome. They also identified chromatin accessibility sites that may be associated with disease.
3. In-depth interpretation of Nature papers! The most detailed cellular and molecular map of the human heart has been constructed to help develop personalized heart disease treatments
doi:10.1038/s41586-020-2797-4
The new research comes from Harvard Medical School, Brigham and Women's Hospital, Welkom Foundation Sanger Research Institute, Imperial College London, and Max Delbrück Center for Molecular Medicine in Germany. Institutional researchers have constructed a detailed cellular and molecular map of a healthy human heart to understand how this vital organ functions and to clarify the problems of cardiovascular disease. The relevant research results were published online in the journal Nature on September 24, 2020, with the title of the paper "Cells of the adult human heart".
These authors analyzed nearly 500,000 cells and established the most comprehensive map of human heart cells to date. The map shows the huge diversity of cells and reveals the types of cardiomyocytes, cardioprotective immune cells, and intricate blood vessel networks. It also predicts how these cells communicate to keep the heart working properly.
This research is part of the "Human Cell Atlas" project, which aims to map every cell type in the human body. New molecular and cellular knowledge about the heart is expected to give people a better understanding of heart disease,And guide the development of highly personalized treatment methods. These authors stated that this research also laid the foundation for the development of regenerative medicine-based therapies in the future.
4. Nat Med: Reveal the single-cell atlas of the peripheral immune response of patients with severe COVID-19 !
doi:10.1038/s41591-020-0944-y
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2, and it is currently close to 800 worldwide. Ten thousand people are infected, and there is an urgent need to further understand its pathophysiological characteristics. About 20% of COVID-19 patients develop severe illness, and 5% of patients require intensive care. Severe diseases are related to changes in peripheral immune activity, including the increase of pro-inflammatory cytokines, which may be caused by inflammation monocyte , lymphopenia and T cell failure, but the specific situation is still unclear.
Image source: Nature Medicine.
In order to clarify the peripheral immune cell pathways that may have a protective effect or cause disease in patients with severe COVID-19, recently researchers from Stanford University School of Medicine in the Department of Medicine and Stanford Medical Scientist Training Program Angela J. Rogers and Under the leadership of Professor Catherine A. Blish, single-cell RNA sequencing (scRNA-seq) was applied to the peripheral blood samples of 7 hospitalized COVID-19 patients (including 4 patients with acute respiratory distress syndrome) and 6 healthy participants. Nuclear cells (PBMCs) were tested,Related research results were recently published in Nature Medicine, entitled "A single-cell atlas of the peripheral immune response in patients with severe COVID-19".
Researchers found that in COVID-19 patients, peripheral immune cell phenotypes are remodeled, including heterogeneous interferon-stimulated gene signals, HLA class II down-regulation, and plasma mothers in patients with acute respiratory failure who require mechanical ventilation. Cells are closely related to the developing population of neutrophils. Importantly, the researchers found that peripheral blood monocytes and lymphocytes do not express large amounts of pro-inflammatory cytokines.
5. Nature: Zhejiang University leads significant progress in constructing a comprehensive human single cell map
doi:10.1038/s41586-span-0203span _strong doi:10.1038/s41586-span-0203span 4 In a new study, researchers from research institutions such as Zhejiang University in China have taken a big step towards building a comprehensive human single-cell map. The relevant research results were published online in Nature on March 25, 2020. The title of the paper is "Construction of a human cell landscape at single-cell level". In this paper, they described how they sequenced the RNA of more than 500,000 cells donated by volunteers and how to process this information to display it in a way that can be used for single-cell maps.
All cells in the human body have the same genetic information,But they differ in which genes they express. Those genes expressed determine the function of a given cell. For some time, medical researchers have wanted a map that can describe which genes are expressed in cells in various parts of the body. Such an atlas will help scientists better understand the functions of cells and how they work together, and can also save time for new research work. People have constructed cell maps for certain tissue types, but currently, no single map can cover all cell types in the human body. After all, since the human body has more than 30 trillion cells, it takes a lot of time and effort to construct such a map. In this new study, these researchers have taken a big step towards this goal, providing gene expression information for more than 500,000 cells (including all major organs) in different parts of the human body (including fetal tissue).
6.Science: Constructing the first human thymocyte map, revealing the origin of the human immune system, and opening the door for the development of new cancer immunotherapies
doi:10.1126/science.aay3224 _span0 span The first cellular map of the human thymus may lead to new immunotherapies to treat cancer and autoimmune diseases. Now, in a new study, researchers from the University of Newcastle in the United Kingdom, the Welkom Foundation Sanger Institute, and , Ghent University in Belgium and other research institutions have drawn a map of the thymus tissue in human life. To understand how it develops and produces important immune cells called T cells. In the future, this information may help scientists construct artificial thymus and design improved therapeutic T cells. The relevant research results were published in the Science Journal on February 21, 2020. The title of the paper is "A cell atlas of human thymic development defines T cell repertoire formation".
These researchers used single-cell technology to isolate and analyze approximately 200,000 cells from the developing thymus and thymus tissues of children and adults. They studied the active genes in each cell to identify these cells. As a result, they discovered new cell types and used these genes as markers to map each cell to its exact location in the thymus.
, the first author of the paper, Dr. Jongeun Park of the Wellcome Foundation Sanger Institute, said, “We have drawn the first human thymocyte map to understand healthy thymus throughout the life cycle from development to adult What happened and how it provides an ideal environment for supporting T cell formation. This publicly available resource will enable scientists around the world to understand how the immune system develops to protect our body."
7 .Nature: Draw the cell map of the developing human liver for the first time, deciphering the secret of human fetal liver hematopoiesis
doi:10.1038/s41586-019-1652-y
For the first time in the world, British researchers have constructed a cell map of the developing liver in humans, which provides important insights into how the blood and immune system in the fetus are produced. This map depicts changes in the cellular landscape of the developing liver between the first trimester and the second trimester of pregnancy, including how stem cells from the liver are seeded into other tissues to support the high oxygen demand required for growth . Related research results were recently published in the journal Nature, with the title of the paper "Decoding human fetal liver haematopoiesis".
This map is a comprehensive high-resolution resource,It can improve our understanding of normal development and help medical institutions treat diseases that may develop during development, such as leukemia and immune diseases.
8.Science: The first human kidney immunity map was drawn
doi:10.1126/science.aat5031
recently drawn a recent study of from 70. After the kidney cell maps of living and adult individuals, the first human kidney immune system map was created. This study was done by researchers from University of Cambridge, Wellcome-Sanger Research Institute and other institutions. It shows for the first time how our kidney immune system develops as early as the embryonic period, and how it develops after birth and adulthood. Gradually increasing. The results, published in the journal "Science", open the door to understanding how the kidney immune system works, and are of great significance for solving many types of kidney disease and transplant rejection.
Image source: CC0 public domain.
In order to understand the kidney's immune system, what happens when tissue damage or infection occurs, how it leads to chronic kidney disease, and the reasons for rejection of a kidney transplant, researchers have drawn the first map of the kidney immune system. In order to create an atlas of kidney cells at different developmental stages, they studied developmental, child and adult kidney tissues. The team used single-cell RNA sequencing to sequence the gene activity in 67471 individual cells to find out the types of immune cells present. Then, they took these cells throughout the development process from early life to adulthood,And draw in the anatomical space of the kidney to understand how the immune system of the kidney develops and matures.
The researchers found that the earliest cells in the developing kidney are macrophages , which are large white blood cells that eat harmful bacteria and viruses. They remain in the kidney as they age. There are few active immune cells in the developing kidney, which is consistent with the view that developing babies are relatively sterile and only encounter bacteria at birth and after birth, which promotes the development of the immune system as we grow.
9.Science: Constructed a cell map of the complete life cycle of Plasmodium --- Malaria cell map, which greatly accelerates malaria research and therapy development
strong7:10.1span doi.i aaw2619; doi:10.1126/science.aay5963
In a new study, researchers from the United Kingdom, Denmark , Kenya, South Africa, Australia, Sweden and France constructed a Malaria Cell Atlas (Malaria Cell Atlas), this map presents the transcriptomic characteristics of the malaria parasite in all morphological life cycle stages. The goal of this map is to (i) understand the function and use of genes throughout the life cycle; (ii) understand the gene regulation mechanism behind the transition of developmental stages; (iii) discover the bet-hedging pattern of malaria parasites; (Iv) Provide a reference data set that can be used to understand the biological characteristics of parasites of various Plasmodium species in the laboratory and under natural infection. The relevant research results were published in the Science Journal on August 23, 2019. The title of the paper is "The Malaria Cell Atlas: Single parasite transcriptomes across the complete Plasmodium life cycle".
These researchers isolated 1,787 Plasmodium parasites by using cell sorting methods, and analyzed their full-length transcriptomes at 10 time points covering all life cycle stages in mosquitoes and mammalian hosts.
From these data, they were able to understand the fine transcription patterns of development and identify marker genes related to the malaria parasite stages, cellular strategies (proliferation, growth, and sexual stages) and host environment. A comparison of single-cell gene expression patterns throughout the life cycle revealed that several groups of genes have similar expression patterns during development. The resulting gene clusters with similar behavior can infer the possible functions of approximately 40% of the genes that are still uncharacterized.
Using droplet sequencing, the researchers sequenced another 15,858 cells from the developmental cycle of red blood cells from three Plasmodium species (including two human Plasmodium pathogens). They compared the developmental trajectories of these three Plasmodium species at the pathogenic stage of the life cycle and established a cross-species comparison method. Finally, they developed an experimental protocol for preserving wild malaria parasites collected from natural infected carriers, using scRNA-seq for sequencing, and using the malaria cell map as a reference to identify the developmental stage of wild malaria parasites. Characterize natural mixed species infections at single cell resolution.
10. Nature: Significant progress! Constructed a complete cell map of the human liver and identified a new hepatocyte subtype
doi:10.1038/s41586-019-1373-2
Now, in a new study, Researchers from the University of Freiburg, Germany, the Max Planck Institute for Immunobiology and Epigenetics, and University of Strasbourg, France, provided a complete cell map of human liver tissue.Using the so-called single-cell RNA sequencing technology, the Dominic Grün team of the Max Planck Institute for Immunobiology and Epigenetics and the Thomas F. Baumert team of the University of Strasbourg successfully constructed healthy human liver cells A detailed map of the group. Based on the analysis of 10,000 cells from 9 human donors, this cell atlas shows all important liver cell types, including hepatocytes (hepatocytes, the main metabolizing cells in the liver), vascular endothelial cells, and liver cells. It retains macrophages and other immune cell types, as well as bile duct cells and liver epithelial progenitor cells. Using these data, people can capture the diversity of cell types and cell states with unprecedented resolution and understand how they change during development or disease progression. The relevant research results were published online in Nature on July 10, 2019, with the title of the paper "A human liver cell atlas reveals heterogeneity and epithelial progenitors".
These researchers have also discovered an amazing diversity in so-called individual cells of the same cell type. They discovered new subtypes of liver parenchymal cells, vascular endothelial cells and macrophages: although their appearance is almost the same, they have different gene expression profiles. These findings were made possible by significant advances in experimental and computational single-cell analysis methods, which can detect cells at high resolution.
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