Researchers have discovered important new information regarding how DNA is organized spatially within the cells of early embryos. When an embryo first forms after fertilization, each cell has the capability to develop into any type of cell found in the body. The team has focused on the unique spatial arrangement of DNA that occurs at these initial stages of development.
A research team from the Kind Group has made significant strides in understanding the spatial arrangement of DNA within the cells of early embryos. As soon as an embryo forms post-fertilization, cells possess the ability to specialize into any cell type within the body. Their investigation centers on the distinct DNA organization characteristic of these early developmental phases. The findings were published in Nature Genetics on September 16th, 2024.
Every cell in our body carries the same DNA. This DNA holds the genetic information that acts as a blueprint for crafting the proteins essential for cell operations. Despite sharing identical DNA, cells activate only certain segments of it, leading to the development of varying cell types that fulfill diverse functions. This is particularly critical during embryo formation, where each newly formed cell has the potential to evolve into any cell type, like brain or placenta cells.
DNA arrangement within the nucleus
DNA resides in the cell nucleus, where it is folded into active and inactive areas. Typically, regions of DNA situated at the periphery of the nucleus are more densely packed and inactive. This spatial arrangement is vital as it determines which sections of DNA are active, differing from one cell type to another, such as between blood and brain cells. In cells with specific roles, certain parts of the DNA alter their packaging and arrangement within the nucleus, activating or deactivating particular genes. These adjustments define which genes are expressed and shape the cell’s identity. The set of processes influencing gene activity without altering the DNA itself is referred to as the cell’s epigenome. While researchers have extensively explored DNA’s spatial organization, the initial establishment of this organization during embryonic development remains largely ambiguous.
Distinct DNA arrangement in early embryos
To deepen their understanding of embryo development, the researchers aimed to investigate how the epigenome influences DNA organization. In a prior study, the Kind group revealed that during the early days of embryo formation, the positioning of DNA regions near the nuclear edge is distinctly unusual. This unusual positioning may clarify the flexibility of those initial cells in becoming various cell types. Isabel Guerreiro, co-first author of the study, states, “Our objective was to determine the factors leading to the unusual positioning of DNA regions at the nuclear edge during the initial phases of mammalian development. This is often challenging, as we can only gather limited cells from early embryos.” To conduct their analysis, the team employed techniques they had previously established, which allowed them to examine the spatial DNA organization in individual early embryonic cells.
Reasons behind unique DNA organization in early embryos
Utilizing these advanced techniques, known as scDam&T-seq and EpiDamID, the researchers discovered that regions of DNA not positioned near the nuclear edge display elevated levels of a specific modification in the proteins that the DNA wraps around. “This indicates that the presence of this modification deters DNA regions from migrating to the nuclear edge,” Guerreiro explains. “However, it is not only the presence of this protein modification that dictates DNA region locations. We identified that the interplay between the ‘repelling’ protein modification and the intrinsic attraction of the DNA sequence to the nuclear edge plays a crucial role in shaping the unusual DNA arrangement in the cell nucleus of early embryos.”
Insights into embryo development
The researchers have identified a key factor influencing the unconventional spatial organization of DNA within early embryonic cell nuclei. These discoveries mark a significant advancement in understanding healthy embryo development and the processes that allow these cells to differentiate into a myriad of cell types. Guerreiro emphasizes: “Revealing the mechanisms underlying the unique nuclear structure that characterizes the early embryo could enhance strategies in regenerative medicine and improve outcomes in human in vitro fertilization.”
