How the human embryo develops is a complex and unclear phenomenon. Scientists are faced with many challenges when it comes to studying the human embryo, mostly due to ethical restrictions. In a recent study, scientists performed whole-genome sequencing of tissues from adult cells to investigate human embryonic development.
Human Embryogenesis
An adult human body comprises of trillions of cells with over 200 different cell types. How a human develops from a single fertilised embryo to a fully grown adult remains a fundamental unanswered question in biomedical science. Researchers’ understanding of this process remains largely unknown due to the ethical challenges of performing such studies on human embryos.
How sequencing adult cells provided insights into embryogenesis
In a recent study, published in Nature, a team of researchers at the Korean Advanced Institute Of Science And Technology (KAIST) overcame some of these challenges by analysing genetic mutations in cells taken from adult human postmortem tissue. The team explored 334 single cell colonies and performed targeted deep sequencing of 379 bulk tissues. They took samples from several different anatomical locations from seven recently deceased adult donors.
The research team wanted to identify mutations that occurred spontaneously in the early development of cell division. These mutations, known as genomic scars, can act as a genetic blueprint to trace the embryonic development process. To identify the cells with these genomic scars, the team carried out a single-cell clonal expansion. This experiment provides the most sensitive and precise mutation data at the single-cell level. Once the cells with genomic scars were identified, the team then carried out whole genome sequencing (WGS) on each clone.
What they found out about human embryogenesis
The results from the WGS revealed several characteristics of the human embryonic process. Firstly, the team found that mutation rates were higher during the first cell division but decreased by approximately one mutation per cell division. Next, the results indicated that early cells contributed unequally to the formation of the embryo. This meant that at the two-cell stage, one cell had more progeny than the other cell. Interestingly, this process varied between individuals as the ratio of cell progeny was different in each donor.
Moreover, this study allowed the researchers to deduce the time at which cells began to differentiate into different cell types. The team found that embryonic cells were distributed asymmetrically into different tissues, forming the body’s left and right sides. This process was then followed by the cells differentiating into one of the three germ layers. The next stage for these cells was to differentiate into specific tissues. The team also found that a few ancestral cells appeared, which subsequently contributed to the adult cell pools in the blood and the liver.
Future applications
The team hope that, in the future, scaling their approach and increasing the number of samples from different tissues will allow them to study later stages of embryology. Furthermore, they hope that this study will provide the foundation for future studies to complete cellular phylogenies in human embryogenesis.
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