A collaboration between researchers at the Genome Institute of Singapore (GIS) and the Scripps Research Institute (TSRI) has resulted in a detailed map that displays how the human genome is altered during embryonic development. The research is part of an international effort to understand how stem cells differentiate in distinct organs.
The study, titled “Dynamic changes in the human methylome during differentiation,” was published in Genome Research on Feb. 4.
Senior author and senior group leader at the GIS Chia-Lin Wei said in a press release, “In this study, we mapped a major component of the epigenome, DNA methylation, for the entire sequence of human DNA, and went further by comparing three types of cells that represented three stages of human development: human embryonic stem cells, human embryonic stem cells that were differentiated into skin-like cells, and cells derived from skin.”
DNA methylation causes precise subunits of DNA to be chemically changed, which directs which areas of the genome are active and which ones are inactive. This process is critical to embryonic cells transformation from pluripotent stem cells to differentiated ones.
“Epigenetics is the process that determines what parts of the genome are active in different cell types, making a nerve cell, for example, different from a muscle cell,” said TSRI Professor Jeanne Loring, co–senior author of the paper.
The researchers collected data on the methylation of three billion base pairs of DNA, which made it possible to classify unidentified patterns of DNA methylation. They distinguished cases where DNA methylation enhanced, rather than suppressed, the activity of the surrounding DNA, and discovered evidence to infer a role for DNA methylation in the regulation of mRNA splicing.
“We produced a very large amount of data,” said study author Louise Laurent, of Scripps Research. “But it actually simplifies the picture. We identified patterns of many genes that are methylated or demethylated during differentiation. This will allow us to better understand the exquisitely choreographed changes that cells undergo as they develop into different cell types.”
Grants for the study was provided by the National Institutes of Health, the California Institute of Regenerative Medicine, Agency for Science, Technology and Research (A*STAR) of Singapore, and The Esther B. O’Keeffe Foundation.
