In his quest for knowledge, to capture the essence of the human being in a precise and objective way, Leonardo da Vinci regularly attended numerous dissections to study our anatomy. During them, between 1510 and 1512, he drew in private notebooks his famous red and black sketches of the development of the fetus.
He was the first to represent it correctly placed inside the uterus, formed by a single chamber, when it was thought that it had more than one compartment. He also reproduced the uterine artery or umbilical cord vessels in detail, with cross-sectional diagrams and views from multiple angles, as is still done today.
Although I insisted on the importance of lenses to observe our surroundings, Da Vinci did not know the microscope nor is it contemporaneous with the discovery of the cell, which came a century later. The understanding of embryology has come a long way since the Renaissance.
However, only until this week have we known, for the first time, all the events that occur in the human embryo between days 16 and 19 after fertilization. Five centuries later, the results are not only unprecedented, but surprising.
A group of scientists from the University of Oxford (United Kingdom) has waited patiently for the donation of a living human embryo of this age to study it. The legislation of the United Kingdom, as in Europe, only allows it to be done in vitro until the 14th day, so all the information we have about what happens in the third week of development comes from human histological samples, from other species. (monkey, mouse, …) or artificial embryos formed in the laboratory.
A lot is known about the process, but not everything, and we talk about crucial information to understand which cells originate, when they do it or where they come from. They depend on it future research to prevent the death of a fetus or cure diseases.
The study, published this Wednesday in the journal Nature, has been made with a single specimen, a healthy male embryo, between 16 and 19 days old, donated during the interruption of a pregnancy to the British institution Human Development Biology Resource (HDBR), which coordinates the informed consent and the ethical issues of the procedure. “The greatest difficulty was obtaining the precious sample,” Shankar Srinivas, professor of developmental biology at the Department of Physiology, Anatomy and Genetics at the University of Oxford and co-director of the work together with Antonio Scialdone, researcher at the Institute of Epigenetics and Stem Cells from the Helmholtz Center in Munich, Germany.
“This is the only sample of this early stage of development that we have received from HDBR in more than five years,” said Srinivas. The development phase analyzed corresponds to that of the third week of gestation, which is known as Carnegie stage 7, at which time the embryo gastrulation occurs.
This means that the cells, whose function cannot be distinguished, move forming like a fold that places them in three different layers (an outermost or ectoderm; another innermost or endoderm; and another in the middle, mesoderm). Each of them form different types of cells, which in turn will give rise to different tissues and organs, until a complete individual is formed.
Using the single-cell RNA sequencing technique, Srinivas and his colleagues have seen these three layers form, identifying all the types of cells that constitute them and seeing which genes are active at any given moment. Thus they have established the sequence of what happens in this embryo, step by step, cell by cell, gene by gene.
And what they have observed, although they intuit something from what is already known about dissections, histological sections or in vitro models, they were not expecting it. Of the RNA analysis of 1,195 individual cells they have identified about 4,000 genes per cell and with them they have differentiated 11 cell populations.
Populations are said because some cells are generated from others and can constitute different stages of the same cell type. That’s what it’s about see the lineage and what each one does of these cells in such early stages of development.
“It was a surprise to see red blood cells so early”, Srinivas stressed. This is one of the most important results of the work.
“We see many different types of blood cells, both red blood cells and the type of white blood cells,” he clarified. These blood cells, as you have found, they do not come from the mother.
Furthermore, when comparing it with what occurs in other animals, such as the mouse, they have seen that hematopoiesis (the formation of blood cells)occurs earlier in humans. Another of the results is very significant for the opposite: because it is not.
Between days 16 and 19 and for this single individual have not observed the activity of any of the genes in the nervous system. This means that neural tissue formation occurs later.
If this fact is corroborated, there could be achange in international norms of biotics, restricting research with human embryos from day 14. “As for the nervous system, we don’t know what to expect, as there is very little human data available at these stages. The fact that we don’t see any neurons at this stage indicates that they are not yet in place to receive sensations. This it may be something to keep in mind when reviewing the ’14 day rule’ regarding human embryo culture, “Srinivas said.
And finally, although the amount of information generated is enormous and opens up many lines of investigation, this look at the “forbidden week” confirms a piece of information that was only half known. Germ line cells have been found,future sperm (Remember that the sex of the sample is male), which is consistent with the in vitro finding of these cells in human embryos of only eleven days.
“Others had already reported the presence of primordial germ cells (PGCs) in cultured embryos or non-human primate embryos in these early stages, so it was not a surprise. However, it was important to verify that PGCs are also present in uncultured human embryos, which our study does, “concluded Srinivas. These data are very useful in biomedicine and in vitro fertilization techniques.
They also serve to refine in vitro models of human embryos and they open the door to future research with diverse genetic and pharmaceutical applications. For its part, the Srinivas group wants to continue in basic science, comparing human embryonic phases with those of the mouse, to see what the equivalent cells are and how when they migrate through different routes.
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