Scientific Updates

Cell | Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development

  On Feb. 4th, 2021, the Xie Lab from Biomedical Pioneering Innovation Center (BIOPIC) and Beijing Advanced Innovation Center for Genomics (ICG) in Peking University, collaborating with Dr. Longzhi Tan from the Department of Bioengineering, Stanford University, published a paper entitled “Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development” in Cell, which uncovers an unknown dimension of neurodevelopment.

  Dynamic, cell-type-specific regulation of 3D chromatin structure is extremely essential for the proper development of the human brain. Both three-dimensional (3D) genome structures and transcriptome play critical roles in neurodevelopment and disorders. However, little is known about single-cell transcriptome and 3D genome dynamics after birth. In this study, the research group provides a comprehensive 3D-genome (3,646 cells) and gene expression atlas (3,517 cells) of the developing mouse cortex and hippocampus with single-cell resolution using the high-resolution MALBAC-DT and Dip-C methods and developing multi-omics analysis pipelines1,2. Both transcriptome and 3D genome are extensively transformed during development in the first post-natal month.


  First, the research group answers a fundamental question in cell biology: Do different cell types/sub-types also have distinct, underlying 3D genome “structure types”? In adults, by multi-omics integration of the group’s and public databases, the researchers conclusively show that 3D genome ‘structure types’’ alone can unbiasedly separate single cells across neuronal and glial sub-types, with high correlation between chromatin A/B compartments and gene expression, refuting a recent conclusion from a low-resolution single-cell Hi-C study3.


  Finally, the research group leverage Dip-C’s superior allelic resolution to answer an important question in developmental biology: Do allele-specific 3D genome structures underlie genomic imprinting? The researchers perform a genome-wide 3D analysis of all imprinted genes and observe parent-of-origin-specific structures for at least 7 of the 29 imprinted gene clusters. Most surprisingly, allelic difference extends tens of megabases (Mbs) to nearly the entire Chr 7, from the Prader-Willi/Angelman syndrome (PWS/AS) locus.


  Dr. Longzhi Tan is the first author of the paper. Prof. Xiaoliang Xie and Dr. Longzhi Tan are the co-corresponding authors of the paper. This work was supported by Beijing Advanced Innovation Center for Genomics at Peking University. 

  1、Tan, L., Xing, D., Chang, C. H., Li, H. & Xie, X. S. Three-dimensional genome structures of single diploid human cells. Science 361, 924-928, doi:10.1126/science.aat5641 (2018).

  2、Chapman, A. R. et al. Correlated Gene Modules Uncovered by Single-Cell Transcriptomics with High Detectability and Accuracy. bioRxiv, 2019.2012.2031.892190, doi:10.1101/2019.12.31.892190 (2020).

  3、Lee, D.-S. et al. Simultaneous profiling of 3D genome structure and DNA methylation in single human cells. Nature Methods 16, 999-1006, doi:10.1038/s41592-019-0547-z (2019).