11 June 2020

Gastruloid

Scientists have assembled a model of a human embryo from stem cells

RIA News

British and Dutch biologists have created a model from stem cells to study the early stage of human development. The study is described in the journal Nature (Moris et al., An in vitro model of early anteroposterior organization during human development).

Researchers from the University of Cambridge in the UK, in collaboration with colleagues from the Habrecht Institute in the Netherlands, have assembled a three-dimensional model from human embryonic stem cells that resembles the location of its key elements of a human embryo aged 18-21 days.

The model, called a gastruloid, consists of three layers organized according to the early plan of the human body. The body plan arises in the process of gastrulation, when the first signs of differentiation appear – the emergence of structural and functional differences between individual cells and parts of the embryo.

gastruloid.jpeg

Green – the back part, similar to the tail part of the embryo; purple – the front part, similar to developing heart cells; gray marks – DNA. Drawing from the press release of the University of Cambridge Human embryo-like model created from human stem cells – VM.

During gastrulation, three separate layers of cells are formed in the embryo, which later form all the main systems of the body: the ectoderm creates the nervous system, the mesoderm creates the muscles, and the endoderm creates the intestines.

Gastrulation is often referred to by scientists as the "black box" period of human development – it is impossible to observe it in the laboratory, because legal restrictions do not allow growing human embryos older than 14 days in vitro.

But many birth defects manifest themselves precisely at the stage of gastrulation, including those associated with the effects of alcohol, drugs, chemicals or infections on the fetus. A better understanding of the processes of this stage, according to the authors of the study, will shed light on many medical issues, including infertility, miscarriage and genetic disorders, and develop appropriate tests for pregnant women.

The study of laboratory animals, such as mice and danio fish, previously allowed scientists to gain some insight into the processes of gastrulation, but the embryos of these organisms behave differently than human embryos and react differently to drugs. Therefore, it was important to develop a human model of development, the scientists note.

"Our model is part of the human plan," the words of the head of the study, Professor of the Department of Genetics Alfonso Martinez–Arias (Alfonso Martinez-Arias) are quoted in a press release from the University of Cambridge. – It is interesting to observe the development processes that have been hidden from the eyes and inaccessible to study until now."

To create a gastruloid in the laboratory, scientists placed a certain number of human embryonic stem cells in small wells, where they formed dense aggregates. The analysis of chemical signals showed that the elongation of all aggregates, including genetic chains, occurs along the anterior-posterior axis, which determines the position of the "head" and "tail" in accordance with the mammalian body plan.

By looking at which genes were expressed at 72 hours of development, the researchers found a clear differentiation leading to the appearance of important body structures such as pectoral muscles, bones and cartilage.

"This is an incredibly exciting model that allowed us to identify and investigate the processes of early human embryonic development in the laboratory for the first time," says lead author Naomi Moris, a geneticist at the University of Cambridge. "Our system is the first step towards modeling the appearance of the human body plan and may be useful for studying what happens when something goes wrong, for example, with birth defects."

The authors note that their experiments are absolutely safe and comply with current ethical standards. Gastruloids are not able to develop into a fully formed embryo. They don't have the brain cells or tissues needed for implantation into the uterus, so they will never be able to advance beyond the earliest stages of development.

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