Chinese scientists have successfully drawn a developmental map of the human immune system
Reporters learned from the Chinese Academy of Sciences Shenzhen Institute of Advanced Technology on September 14 that Chinese scientists have recently successfully mapped the development map of the human immune system, which is characterized by wide tissue coverage, long time span, high sampling density, and is expected to promote the development of global immunology and developmental biology. The research findings have been recently published in the international academic journal Cell.
As the "guardian" of preventing viruses, bacteria and other pathogens from invading the human body, immune cells are an indispensable component of the immune system. Clarifying the type, differentiation, and functional status of immune cells is of great significance for understanding immunity and revealing the mechanisms of immune related diseases.
Han Jiahuai, an academician of the CAS Member and a professor of Xiamen University, said that this research has expanded people's understanding of human immune development, helped to deeply understand the function and regulation mechanism of the immune system, and laid an important foundation for disease diagnosis, immunotherapy and the development of new therapies.
The research was jointly completed by Shenzhen Advanced Technology Research Institute of the Chinese Academy of Sciences, Shenzhen Bao'an Maternal and Child Health Care Institute, Shenzhen University, Shanghai Jiaotong University, Fudan University, etc.
A schematic diagram of scientific research achievements: The plot of Sun Wukong monkey hair transforming into multiple monkeys, symbolizing the differentiation of macrophage precursors derived from yolk sac into different cell subpopulations. Research team provides images
Decoding 300000 cells to construct an immune cell map
At the beginning of the non-stop operation of the human body, immune cells begin to rapidly proliferate, differentiate, and migrate, providing a unique time window for studying the formation and development of immune characteristics in tissue and organ regions. In this study, the team used a self-developed single-cell transcriptome sequencing platform to "decode" 300000 developing immune cells, successfully constructing a high-resolution human immune system development map with the widest tissue scope, the largest time span, and the highest sampling density in the research field.
"We conducted undifferentiated single cell transcriptome sequencing on a large number of samples. The advantage of this technology is that when we do not know which cell subtype the sample is, we can directly infer the cell type from its gene expression profile, so that we can better find the unknown cell group." said Li Hanjie, the corresponding author of the paper and the Institute of Synthetic Biology of the Chinese Academy of Sciences Shenzhen Institute of Advanced Technology.
The research team identified 11 main types of immune cells, classified each type in more detail, and finally annotated 56 subtypes of immune cells, including 15 macrophages, and accurately depicted their spatiotemporal dynamic changes in the map.
Li Hanjie introduced that the research team has developed a shared visualization platform for this graph, and the relevant data can be publicly queried, so that more researchers can explore this dataset and jointly promote the development of immunology research.
Discovering new types of cells refreshes scientific understanding
Macrophages are a widely distributed and versatile member of the immune system. They are both the "cleaning teams" of the body, clearing pathogens and harmful substances by devouring cell debris and waste; At the same time, it is also a sentinel of the immune system, which releases signals such as cytokines to inform other immune cells of foreign invading substances and prepare them for battle. In addition, macrophages can also perceive changes in the surrounding environment and maintain the body's homeostasis according to the needs of organs.
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Microglia, as the main macrophages in the central nervous system, are traditionally only present in the brain and spinal cord and do not appear in other organs or tissues. Looking at it now, that's not the case.
The research team observed that during development, there is a special subset of cells with a morphology, characteristic protein expression, and transcriptome expression profile that is very similar to microglia, widely distributed in multiple tissues outside the central nervous system. The research team named them "microglia like cells".
"The discovery of microglia like cells will break the inherent belief that 'microglia only exist in the central nervous system'," said Li Hanjie.
So, what are the functions of the newly discovered immune cell types?
Due to the enrichment of microglia in the epidermis, the research team further investigated their function in epidermal tissue and found that microglia are mainly concentrated in the embryonic back, exhibiting a similar distribution pattern to neural crest cells. Experimental evidence has shown that during the development of neural crest cells into melanocytes, the epidermal microglia play a regulatory and controlling role.
"Interestingly, we have also identified a group of macrophages with high expression of pro angiogenic genes in multiple tissues, and have similar gene expression profiles in different tissues, all located near the blood vessels of embryonic organs." Li Hanjie said that the research team has also verified in vitro experiments that this group of cells has the ability to promote angiogenesis and named them "pro angiogenic macrophages".
This type of cell has a highly similar gene expression pattern to angiogenic cells in tumors, which may provide new ideas for the study of tumor pathogenesis and the development of potential treatment strategies.
This study greatly expands the "skill points" of macrophages: they not only have the functions of phagocytosing foreign objects and maintaining homeostasis in the body, but also can affect the differentiation of human neural crest cells during embryonic development, helping to induce angiogenesis and other "innovative" functions.
"This work provides useful guidance for the occurrence and development of diseases in relevant regions, the development of immunotherapy and the in-depth research of developmental biology," said Tian Zhigang, an academician of the CAE Member and a professor of the University of Science and Technology of China.