How Embryonic Stem Cells Make Tissue

This seemingly easy question is a mysterious and profound physical transformation of life that scientists have been challenging for hundreds of years.

How do genes and molecules regulate the strength of tissues and the strength of tissues in a developing embryo to produce a form?

What is the exact mechanism by which the complex organs and tissues encode in our DNA?

Research has been conducted to find answers that are closer to these difficult questions.

A team of biomedical engineering professors at the University of Colorado, Columbia, USA, has published a study in the journal Science, Nature, 16th, that cells will migrate to organs by molecular signals during early embryonic development.

Nandan Nerurkar, assistant professor of biomedical engineering, who led the study, focused his research on specific aspects of embryonic development when he was a postdoctoral researcher at Harvard Medical School.

In other words, how does the stem cell group (endoderm) move from the surface of the developing embryo to the center, and from the flat sheet to the tube with the center hole?

This structure, known as the gut tube, then forms the inner walls of the entire respiratory tract and gastrointestinal tracts.

Molecular signals become long-term formation physical signals

Nerukar, in collaboration with colleagues at Harvard University, presented a new perspective on this important step in early embryonic development.

The researchers found that intestinal formation was induced by the collective cell migration of endoderm. Through this process, cells move at a distance without rearranging their positions.

They have also found that the mass movement of these cells is triggered by cells that convert molecular gradient into force gradient and induce cells inward from the surface of the embryo.

This discovery is one of a few examples of how molecular signals are transformed into physical signals that form our organs, especially among vertebrate animals.

The results of this study are expected to have important implications for how to create functional organs using stem cells in the laboratory. It also helps to understand the underlying causes of congenital gastrointestinal anomalies.

“Our main goal is to understand how complex organisms like human beings are precisely formed from early embryos that are merely circular cells that are not properly organized,” Nerukar said.

Genetic identification, which differentiates stem cells into mature cell types, is the primary goal of Professor Nerukar as an important step toward raising replacement organs in the laboratory.

Nerukar says this is but a part of the whole picture.

“It is equally important to understand how to direct these cells to organize into functional three-dimensional organs.” “Developing embryos have their recipe, and many research groups, including ours, “We are analyzing it by using it.”

Clifford J. Tabin, Ph.D. adviser to Professor Nerukar, who is part of the research team, is Professor of Genetics at Harvard University and Professor L Mahadevan at Harvard University, a professor of applied mathematics and evolutionary biology and physics at the cutting edge of developmental biology. I have used an innovative approach.

They combine engineering approaches such as mathematical modeling and force and strain measurements with traditional developmental biology approaches, including gene expression and cellular real-time time-lapse microscopy analysis and manipulation of cell migration in developing chick embryos.

Microscopic photograph of endoderm cell in chick embryo. Cells visualized with green fluorescent protein (green). The adhesive protein E-cadherin between cells and cells is marked in red. CREDIT: Nandan Nerurkar / Columbia Engineering

The team focused on one part of internalization of the endoderm, the hindgut, which produces the small intestine, the large intestine and half of the colon.

Previously known about bowel tube formation came from fate-mapping experiments. In this map, the cells were mapped to places where the markers were attached at the beginning of development and then later developed.

This static analysis uses static images at the beginning and end of the process to make educated guesses about what happened in the middle, and it shows the time of ministerial formation in most embryology textbooks.

“According to our recent research, this view is incomplete and, in the worst case, it is completely wrong,” Nerukar said.

Unlike initial fate-map studies, Nerukar’s team used images of living embryos to directly observe cell migration when endoderm was internalized and formed the intestinal tract.

Molecule increase turns into a gradient of force

They then combined mechanical engineering and developmental biology approaches to understand how such cell migration occurs and how this movement is regulated to form an important structure in early embryos.

The researchers found that molecular ups and downs translate into a gradient of power coming from the cell, which regulates cell migration. This force is pulled in proportion to the amount of the fibroblast growth factor (FGF) that the cells sense.

This causes tug-of-war competition among endoderm cells. At this point, when a ‘team’ starts to win, the cells reinforce the players by pulling the opponent team players to a higher concentration of FGF at a lower concentration.

FGF irregularities can lead to various developmental defects. Professor Nerukar said, “Errors in the formation of ministers during human development are likely to lead to miscarriage, and the relative risk of abortion during the first trimester of pregnancy is the period during which this process occurs.”

Can be used in regenerative medicine and tissue engineering

This study focused on the posterior gut, which is part of the internalization of the endoderm, but it is not yet clear how the foregut and midgut at the anterior part of the digestive tract form organs. The forehead forms the airways, lungs, esophagus, stomach and liver, and the middle bowel makes the pancreas and small intestine.

Nurukar plans to explore other areas of embryonic development using his new approach. In addition, we will investigate whether fibroblast growth factor (FGF) signals act more extensively and regulate other tissue and organ developmental dynamics.

“I want to learn more about how mechanics and molecules can coordinate and integrate disjointed tissues into a heterogeneous mechanism from the same initial stem cell pool,” he said.

“By focusing on the tissue-level epidemiology of FGF signaling, we are now able to understand how this important pathway develops in other tissues and organs, including the heart, brain and spinal cord, during development.”

Nurukar is currently developing quantitative molecular-dynamics relationships in the laboratory to use in designing and constructing regenerative tissue. Here, signals are used to direct cells to self-organize and form functional tissues and organs by using a controlled delivery of a diffusible signal (an instructional signal that is released by the cell to the neighboring cells).

If he or other researchers can build the design principles of embryo formation, it would be possible to apply the same principles to regenerative medicine and tissue engineering applications.

Hülya Karahan: The Founder

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