Understanding Embryonic Development

New human life is created when a sperm fertilizes an egg. The result is the one-cell embryo or ‘zygote’. This cell has an extremely powerful capacity: it can form a complete organism, a human being from head to toe with all its different cells such as blood, heart, brain, and skin cells.

This amazing capacity is called totipotency. Only the very first cells in the embryo have this capacity because totipotency is lost within just three days after fertilization. Over subsequent cell divisions, the one-cell embryo generates another cell type, which is also of interest to regenerative medicine: the embryonic stem cells. They are no longer able to give rise to a complete body on their own, but they retain an extraordinary potential—they can form any human tissue. By studying stem cells, we can learn from them how they generate all the tissues in our body and we can copy their program to generate cells ‘à la carte’ for regeneration therapies.

Cell reprogramming is a golden opportunity to create "new" cells of any type. Over the last two decades, researchers have been working primarily with embryonic stem cells and with induced pluripotent stem cells (iPS cells). The latter can be induced from any of our adult cells alleviating the ethical concerns arising from the use of human embryos to generate stem cells. The starting point is, for example, a skin cell, which is then reprogrammed into a stem cell. This method was revolutionary because it allows us to produce stem cells from any kind of patient cells. It has nonetheless one drawback: the success rate and the number of stem cells produced are low.

The process of cell reprogramming at the beginning of life is, on the contrary, extremely efficient. If we succeed in copying the capacity of the embryo to reprogram, this truly holds groundbreaking possibilities for cell replacement therapies and regenerative medicine approaches. But how does the embryo acquire the capacity of producing all tissues?

All cells in our body carry the same genetic information: the DNA from our father and our mother. Our DNA contains about 25,000 genes. Each gene serves as a blueprint to generate a protein that can be produced during a process known as gene expression. Theoretically, each cell could express every individual gene to generate all of the possible proteins. However, mass production is not the order of the day here—rather, the cell makes a customized process: each cell produces only the proteins that it needs to fulfill its function. For example, our red blood cells produce hemoglobin, but our neurons do not.

The packaging of the DNA, called the chromatin, controls this process. While some genes have more open chromatin (euchromatin) and are available for gene expression, other genes are packaged into very dense chromatin (heterochromatin). The densely packaged genes are not expressed—thus their information is not ‘read’ and proteins are not generated from them.

Epigenetics is in fact the process that controls the packaging of the DNA and therefore the ‘read’ and ‘not read’ status of a gene. Epigenetics can also change the chromatin at specific genes to ensure that only the required genes of the respective cell type are available for expression enabling the emergence of specific cell types in our bodies.

"Because the DNA content of all our cells is the same, reprogramming must be epigenetic in nature: that means that the identity of the cell changes, but its DNA (genetic make-up) remains identical. The different cell types only vary in the genes that they express, which is largely dictated by the state of the chromatin." Maria-Elena Torres-Padilla.

What We Can Learn From the Embryo

In the last years, the laboratory of Maria-Elena Torres-Padilla and others have revealed crucial findings: the chromatin in totipotent cells of the early embryo differs drastically from the chromatin of differentiated, somatic cells and even from that of pluripotent stem cells. The basis of totipotency can therefore most likely be found within the epigenetic landscape of the early embryo. The embryo is thus a fantastic model to discover the chromatin features that enable totipotency.

The research conducted by Maria-Elena Torres-Padilla's team paves the way for a more efficient and rapid generation of reprogrammed cells—the basis for stem cell therapies. Not all of the processes regulating embryonic reprogramming are known but Maria-Elena Torres-Padilla looks optimistically into the future:

"We still have a lot to learn, but I am confident that if we identify at least some of the natural factors that promote cell reprogramming, we can find ways to use them to reprogram cells in the dish. Our research has already provided evidence that we can do so. This could help to improve cell reprogramming, and make it more efficient and more accessible without the need for any genetic manipulation.”

Latest update: September 2022.