Release date: 2017-11-17

In 1665, Robert Hooke stared at the cork under the microscope, and he saw countless small lattices like rooms. As the first scientist to describe a cell, he will be shocked by what humans are trying to accomplish now—we will use powerful modern genomics and cell biology tools to look at the trillions of cells in the human body.

In 2017, top scientists from around the world announced an ambitious plan to create a Human Cell Atlas. We will decipher the type and characteristics of each cell in the human body and establish a reference map of healthy human cells; we will use it to understand how the human body is formed and why humans are sick; we will have a new and complex biological model to help us improve our research and development. speed.

Without a doubt, we will see something new.

In the journal Nature last week, the Broad Institute research team released the first small intestinal cell map [1]! Based on single-cell RNA sequencing (scRNA-seq), the study determined the expression profiles of a total of 53,193 cells from the gut and gut-like organs of mice, and brought many new discoveries that were different from previous cognitions. The "small intestine encyclopedia".

Focus

1 identified gene expression characteristics of all known cells, specific cell subsets and rare cells in the small intestine

2 Subversion of traditional cognition of intestinal hormone secretion, redefining the classification of enteroendocrine cells

3 Two new cluster cell (Tuft Cell) subtypes were found, which were associated with immune and neurodevelopment, respectively.

4 describes a model of infection of small intestinal cells against parasites and microbial infections, which will provide a theoretical model for intestinal disease research.

The research team was led by Dr. Aviv Regev, co-chair of the International Human Cell Atlas Programme Organizing Committee, MIT Biology Professor, and Dr. Ramnik Xavier, director of the Department of Gastroenterology at Massachusetts General Hospital and clinical gastroenterologist.

Corresponding authors Aviv Regev (left) and Ramnik Xavier (right)

The ability to have such pioneering results also benefits from single-cell sequencing technology (scRNA-seq). In the past, when scientists studied cells, they all sequenced a small piece of tissue. The data thus obtained is only the average score of all cells, and there is no way to reflect the "personality" of each cell. There are many important but small numbers of RNA that can be removed as "highest scores" or "lowest scores" and cannot enter the field of scientists. Single-cell sequencing allows scientists to accurately study the functional changes of individual cells, and what each cell looks like is nothing at all! This technology was named 2013 Annual Technology by Nature magazine.

“The new technology gives us the opportunity to explore cells and tissues in more detail,” Dr. Aviv Regev said. “The new technology allows us to propose new biological issues and examine past research.” [2]

Small intestine cells are "fighting" with parasites

Before detailing this encyclopedia, Singular Cake wants to take everyone back to review the structure of the small intestine.

The small intestine is an important digestive organ of our body. It is followed by the stomach and the large intestine. It also contains important intestinal microbes. The small intestine has a very special place. Its inner surface is not as smooth as the general mucosal tissue, but is covered with "fluff" and has even smaller protrusions on the villi. This special structure makes the internal surface area of ​​the small intestine expand 600 times, and it has 200 square meters! (Sweet cakes are a little envious of intestinal bacteria, live in such a big house... Oh, they have more bacteria, balance)

With such a large contact area, the small intestine has more space to function. The most basic digestion and absorption will not be said, the small intestine can also secrete various hormones to promote various physiological functions, and even participate in immune response.

Structure of the small intestine

So many physiological functions are certainly not a cell that can be achieved. The small intestine cell family is very lively. There are intestinal epithelial cells (Enterocytes) responsible for nutrient absorption, Goblet cells that secrete mucus to protect other members, and endogenous cells (Enteroendocrine cells) that secrete various gastrointestinal hormones. Paneth cells of antibacterial peptides, and tuft cells that have recently entered our field of view.

In this study, the researchers analyzed more than 50,000 cells in one breath, and based on the known signs found in previous studies, continued to search for new markers, and finally successfully identified various types of cells and their The specific expression markers at different stages of maturity have also successfully described super rare M cells! Interestingly, the distribution of cells in the small intestine is not uniform, and different types of intestinal cells play different functions in different regions. For example, in areas close to the stomach, more cells express ghrelin [3] that promotes feeding; on the contrary, cells near the large intestine area are mostly YY peptides that control appetite [4].

Analysis of cell distribution observed by different markers

Using these data, the researchers discovered two previously unrecognized cluster cell subtypes. Cluster cells are a class of cells in the small intestine that can sense chemical signals [5], and recent studies have suggested that they play a key role in defense against parasitic infections [6]. Two newly discovered cluster cell subtypes, one of which is capable of expressing pheromone (Tslp, which promotes immune cell maturation) and the white blood cell common antigen CD45, and the other is related to neural development. This is the first time CD45 has been found on cells outside the hematopoietic system!

In addition, the researchers also proposed a new classification criteria for small intestinal endocrine cells. In the past, scientists believed that an endocrine cell in the small intestine could only secrete a hormone. But the researchers found that in fact these cells are still a lot of versatile, an endocrine cell can actually secrete a variety of hormones, no wonder some studies have not been possible before! They proposed a new taxonomy based on the type of secreted hormone, providing a more detailed theoretical basis for future research.

The vertical axis is the newly classified cell, and the horizontal axis is the secreted hormone.

Legend is the original classification

After taking the "document photo" of the small intestine cells, the "life photos" can not be let go. After all, the human body is dynamic, and the small intestine always faces the threat of foreign pathogens. The researchers used two classical models, Salmonella enterica and Heligmosomoides polygyrus, to simulate the response of small intestinal cells to pathogens and parasites.

In the face of the invasion of pathogens, small intestine cells can be used as a whole body to resist. The researchers observed some up-regulation of protective gene expression, increased expression of multiple antimicrobial peptides, and cells that did not express antimicrobial peptides did not learn this skill. During the infection process, the composition of the small intestine cells also changed, and the number of cells including Paneth cells increased, and the number of stem cells and immature cells decreased, which is consistent with previous studies [7]. Some cells also produce specific expression changes for pathogens, which have never been observed.

Positioning! Nothing to do!

The cells that were invisible to the naked eye are now clearly arranged in front of us. We can see any of them "small movements" and think it is exciting! And this model is dynamic and can be used to test a variety of physiological, pathological and pharmacological processes, which is great news for researchers!

“The intestinal epithelium is linked to both the immune system and the intestinal flora. It is the key to cellular responses. It is important to understand the physiological response of the intestines to health and disease.” The first author of this study, postdoctoral Graduate student Moshe Biton said.

With this data in hand, the researchers will immediately conduct more research, including changes in gut cell gene expression and structural function under various conditions such as Crohn's disease, colitis, gastrointestinal cancer, food allergy, etc. It will give us a better understanding of these diseases, and soon there will be new ways to deal with them~

Source: Singularity Network (micro signal: geekheal_com)

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