British and Dutch scientists have developed a model to study early human development that uses human embryonic stem cells.
Writing in the journal Nature, they say it resembles some key elements of an embryo at around 18 to 21 days old and allows researchers to observe the processes underlying the formation of the human body plan in ways not previously possible.
Understanding these processes, they add, holds potential to reveal the causes of human birth defects and diseases, and to develop tests for these in pregnant women.
“Our model produces part of the blueprint of a human,” says research leader Alfonso Martinez-Arias, who worked with colleagues from the University of Cambridge, UK, and researchers from the Hubrecht Institute in The Netherlands.
“It’s exciting to witness the developmental processes that until now have been hidden from view – and from study.”
Early in development, when the human embryo is a tiny ball of cells, it folds in on itself to form a three-layered structure with a front and a back end called a gastrula.
These layers go on to form the various different tissue types in the body: the ectoderm will make the nervous system, mesoderm the muscles, and endoderm the gut.
Many birth defects originate during this gastrulation process which, the researchers say, is referred to as the “black box” period of human development because legal restrictions prevent the culture of human embryos in the lab beyond day 14, when the process starts.
Animal models have been used to gain some insights into human gastrulation, but these may behave differently to human embryos and respond differently to certain drugs.
The new model uses human embryonic stem cells to generate a 3D assembly of cells, called gastruloids, which differentiate into three layers organised in a manner that resembles the early human body plan. To make gastruloids in the lab, defined numbers of human embryonic stem cells were placed in small wells, where they formed tight aggregates.
After treatment with chemical signals, the gastruloids were seen to lengthen along a head-to-tail axis, known as the anteroposterior axis, turning on genes in specific patterns along this axis that reflect elements of a mammalian body plan.
By looking at which genes were expressed in these gastruloids at 72 hours of development, the researchers found a clear signature of the event that gives rise to important body structures such as thoracic muscles, bone and cartilage.
They stress, however, that gastruloids do not have the potential to develop into a fully-formed embryo. They do not have brain cells or any of the tissues needed for implantation in the womb.