From the Labs: Biomedicine

Three-Dimensional Genome
New technology reveals the higher-order structure of DNA.

Source: “Comprehensive mapping of long-range interactions reveals folding principles of the human genome”
Eric S. Lander, Job Dekker, et al.
Science 326: 289-293

Results: Scientists developed a tool that makes it possible to map the three-dimensional structure of the entire human genome, shedding light on how six feet of DNA is packed into a cell nucleus about three micrometers in diameter. According to the resulting analysis, chromosomes are folded so that the active genes–the ones this particular cell is using to make proteins–are close together.

Why it matters: Growing evidence suggests that the way the genome is packed in a particular cell is key to determining which of its genes are active. The new findings could allow scientists to study this crucial aspect of gene regulation more precisely.

Methods: Scientists treated a folded DNA molecule with a preservative in order to create bonds between genes that are close together in the three-dimensional structure even though they may be far apart in the linear sequence. Then they broke the molecule into a million pieces using a DNA-cutting enzyme. The researchers sequenced these pieces to identify which genes had bonded together and then used this information to develop a model of how the chromosome had been folded.

Next steps: Scientists plan to study how the three-dimensional structure of the genome varies between different cell types, between different organisms, and between normal and cancerous cells. They also hope that improving the resolution of the technology might reveal new structural properties of the genome. They can currently analyze DNA in chunks comprising millions of bases, but they would like to zero in on sequences thousands of bases long.

Diabetic Cells
Stem cells derived from patients with diabetes provide a new model for studying the disease

Source: “Generation of pluripotent stem cells from patients with type 1 diabetes”
Douglas A. Melton et al.
Proceedings of the National Academy of Sciences 106: 15768-15773

Results: Scientists collected cells from patients with type 1 diabetes and turned them into induced pluripotent stem cells, adult stem cells with an embryonic cell’s capacity to differentiate into many different cell types. Then they stimulated these cells to differentiate into insulin-producing pancreatic cells.

Why it matters: The stem cells carry the same genetic vulnerabilities that led the patients to develop diabetes. Watching them develop into insulin-producing cells should shed light on the development and progression of diabetes. Researchers may also be able to test new treatments on the developing cells.

Methods: Researchers “reprogrammed” skin cells from two diabetes patients by using a virus to insert three genes involved in normal development. The new genes caused other genes to turn on and off in a pattern more typical of embryonic cells, returning the skin cells to an earlier developmental stage. The scientists then exposed the cells to a series of chemicals, encouraging them to differentiate into insulin-producing cells.

Next steps: The researchers will examine the interaction between the different cell types affected by diabetes: the pancreatic beta cells and the immune cells that attack them. Initially they will study these interactions in a test tube, but ultimately they hope to incorporate the lab-generated human stem cells into mice. This will help scientists understand which cells are affected first. Armed with that knowledge, they could begin developing treatments that involve replacing some of those cells.