Single-cell multiplex chromatin and RNA interactions in aging human brain

Sheng Zhong, Ph.D.

Professor of Bioengineering

University of California, San Diego

Seminar Information

Seminar Date
May 24, 2024 - 2:00 PM

The FUNG Auditorium - PFBH



Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA. Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells. Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA–chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an ‘older’ transcriptomic signature and Alzheimer’s disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues.

Speaker Bio

Sheng Zhong is a professor in the Shu Chien-Gene Lay Department of Bioengineering at UCSD. He received training in applied mathematics, bioinformatics, molecular biology, and genome science from Peking University, Harvard University, and Stanford University. His lab hopes to develop technologies to reveal all molecular interactions in every cell and combat brain aging. He is fortunate to work with outstanding students and postdocs. Nine of his trainees are contributing to science in tenure-track faculty positions. Outside of the laboratory, he enjoys playing tennis and visiting museums. Despite his admitted lack of musical talent, he harbors a desire to improve his singing abilities in the future.