Revealing the Structure of Human Chromosomes and Nucleus in Three Dimensions

When we talk about chromosomes, the familiar images with an X-shape would probably flash into our minds. Did you ever think that the chromosomes could be in other shapes, not the X-shape, with an organized structure?

A team led by LCN researchers, Prof. Ian Robinson and Dr. Bo Chen, now a professor at the Tongji University in Shanghai, used newly-developed serial block-face scanning electron microscopy (SBFSEM) to reveal the spatial structure of human chromosomes and nucleus quantitatively at high resolution of about 50nm in three dimensions.  

The research found out that the chromosomes are also S-shaped and C- shaped, not only X-shaped, and the larger chromosomes were more likely to be in S shape or C shape, whereas the smaller chromosomes tend to be the familiar X-shape. It also found out that chromosomes are non-randomly positioned in the prophase nucleus with the gene-rich chromosomes near the nuclear centre and gene-poor ones near the periphery. The research team also deduced that the chromatin condenses locally into “visible” chromosomes during the cell cycle. Furthermore, during the chromatin condensation, the sister chromatid pairs were found are not identical in morphology, although the volumes were similar. 

Image: One of the BSE micrographs, from SBFSEM, of the human nucleus (left); 3D structure of the human nucleus, with its envelope in light blue and the chromosomes in colour (right)

From the quantitative analysis of the obtained 3D structure of chromosomes, the volume of base pair was calculated to be 6.69 nm3, and the sister chromatids have a well-conserved diameter of about 765nm in cylindrical shape regardless of their sizes. The research team also proposed a potential new method for identifying human chromosomes, in three dimensions, based on the analysis of their 3D morphology and sizes, but not conducting the multicolour fluorescence in situ hybridization (M-FISH) measurements as traditionally performed.

The method can be used in the future to identify human chromosomes through 3D imaging approaches.

This work was supported by the Biotechnology and Biological Sciences Research Council (UK), the Engineering and Physical Sciences Research Council (UK) and partially by Tongji University (China).

The authors of this paper have applied the powerful and persuasive method to the biological and biomaterials area and are able to go further in the investigation of the condensation process of the chromatin by comparing the 3D structure of chromosomes and nuclei at the different stages of cell cycle using the newly established SBFSEM facility at the Tongji University, Shanghai.

Link to publication: “Three-dimensional positioning and structure of chromosomes in a human prophase nucleus” Bo Chen, Mohammed Yusuf, Teruo Hashimoto, Ana Katrina Estandarte, George Thompson & Ian Robinson in Science Advances, Biophysics

Other contributors: 
Bo Chen & Mohammed Yusef (former LCN), Teruo Hashimoto & George Thompson (The University of Manchester)