A mathematical framework for the internal design of cells.. an attempt to understand the building blocks of the human cell | Sciences

Understanding how cells self-regulate in health, and the full range of variations found in the ‘normal’ environment, can help scientists better understand what goes wrong in disease.

The cell is the smallest structural unit in the human body, consisting of hundreds of millions of cells that share its structure and components, and differ in their shape, functions and internal organization. Scientists have long been studying the human cell, its shapes and differences. Try to understand the causes, methods and results of the difference.

As part of these efforts, a group of researchers at the Allen Institute for Cell Science were able to quantify the internal organization of human cells, a biological concept that has been very difficult to achieve until today, and they were also able to capture details about The rich variation in cell shape even among genetically identical cells growing under identical conditions, and the researchers published the results of their study in the journal Nature on January 4.

“The way cells are organized tells us something,” says Dr. Susan Rafelsky, deputy director of the Allen Institute for Cell Sciences, who conducted the study with lead scientist dr. led. “What we’ve been missing in this field, where we all try to understand how cells change in health and disease, is a precise way to approach this kind of organization.”

Composite image showing several transgenic cells with fluorescent markers illuminating the internal structures (Allen Institute for Cell Sciences)

road map

“This study provides a road map for biologists to understand the regulation of different types of cells in a quantifiable, quantitative way. It also reveals some key regulatory principles for the cells the Allen Institute team studies, known as induced pluripotent stem cells.” Understanding how cells regulate themselves under healthy conditions—and the full range of variations found in the ‘normal’ environment—can help scientists better understand what goes wrong in disease.

“Part of what makes cell biology so challenging is the fact that every cell looks different, even when they are the same species,” said Dr. This same variation that has plagued the field for so long is in fact an opportunity to study the rules by which cells are assembled. This approach is generalizable to almost any cell, and I expect many others to adopt the same methodology.”

In biology, form and function are interrelated, and understanding cell form is important to understanding how cells work (Getty Images)

high-definition pictures

The work, which began 7 years ago, involved building a group of genetically engineered stem cells, then illuminating the cells’ various internal structures under a fluorescent microscope. By examining the available cell lines, 25 individual cell structures were identified, and the scientists took high-resolution 3D images of more than 200,000 different cells.

The team faced the challenge of comparing the same structure between two different cells. Although the cells studied were genetically identical and grown in the same laboratory environment, their shapes were very different. Scientists realized that it would be impossible to compare the position of structure A in two different cells if one cell was short and compact and the other long and pear-shaped, so they put numbers on that short and long piriformis.

Using computer analysis, the team developed what they call a “shape space” that objectively describes the external shape of each stem cell. This shape space includes 8 different dimensions of shape diversity, such as length, size, elongation, and the appropriate descriptors “pear” and “bean”, which then enabled the scientists to compare apples to apples (or beans to beans). given the organization of cellular structures within all similar cells.

“We know that form and function are related in biology, and understanding cell form is important to understanding how cells function,” says Dr. Viana. “We got a framework that allows us to measure cell shape, and the Once we do that, you can find cells with similar shapes, and for those cells, you can then look inside and see how everything is arranged.”

Scientists examined 25 different structures and compared those structures to groups of cells with similar shapes (Getty Images)

strict regulation

When the scientists examined 25 separate structures and compared those structures to groups of cells with similar shapes, they found that all cells organized their contents in remarkably similar ways, despite the large differences in cell shape, and their internal organization was remarkably consistent. .

Discovering differences from the normal state can give scientists important information about how cells change when they go from stationary to mobile, or when they prepare to divide, or about what goes wrong at a microscopic level during disease. The researchers examined two different types in their data set: cells at the edges of cell colonies, and cells undergoing division, a process known as mitosis. In both cases, the scientists were able to find changes in internal organization linked to the different environments or activities of the cells.

“This study brings together everything we have done at the Allen Institute for Cell Sciences since the institute was launched,” says Dr. Roe Gunordan, executive director of the Allen Institute for Cell Sciences. “We built it all from the ground up, including metrics to measure and compare different aspects of how cells are organized. What I’m really excited about is how we and others in the community can now build on this and can ask questions about cell biology that we couldn’t ask before.”

The image dataset, transgenic stem cells, and symbols entered into this study are all publicly available for use by other scientists.

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