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bioRxiv · 10.1101/2023.06.28.546457

Joint profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations in single cells of the human brain

Luo, Z.·Wen, X.·Zhao, W.·Nguyen, T.·Wan, X.·Richard, J. L. C.·Zhong, S.
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Abstract

SUMMARY PARAGRAPHThe dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA (caRNA) 1-3. Chromatin complex compositions change during cellular differentiation and aging, and are expected to be highly heterogeneous among terminally differentiated single cells 4-7. Here we introduce the Multi-Nucleic Acid Interaction Mapping in Single Cell (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations within individual nuclei. Applied to 14 human frontal cortex samples from elderly donors, MUSIC delineates diverse cortical cell types and states. We observed the nuclei exhibiting fewer short-range chromatin interactions are correlated with an "older" transcriptomic signature and with Alzheimers pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci (cis eQTLs) and a promoter tends to be the cell type where these cis eQTLs specifically affect their target genes expression. Additionally, the female cortical cells exhibit highly heterogeneous interactions between the XIST non-coding RNA and Chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploring chromatin architecture and transcription at cellular resolution in complex tissues.

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Luo, Z., Wen, X., Zhao, W., Nguyen, T., Wan, X., Richard, J. L. C., Zhong, S.. 2023-06-29. Joint profiling of multiplex chromatin interactions, gene expression, and RNA-chromatin associations in single cells of the human brain. https://doi.org/10.1101/2023.06.28.546457

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