Single-cell multiplex chromatin and RNA interactions in ageing human brain.

Autor: Wen X; Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA., Luo Z; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.; Department of Genetics, School of Medicine, Stanford, CA, USA., Zhao W; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA., Calandrelli R; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA., Nguyen TC; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.; Department of Genetics, School of Medicine, Stanford, CA, USA., Wan X; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA., Charles Richard JL; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA., Zhong S; Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA. szhong@ucsd.edu.; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. szhong@ucsd.edu.; Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, USA. szhong@ucsd.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Apr; Vol. 628 (8008), pp. 648-656. Date of Electronic Publication: 2024 Mar 27.
DOI: 10.1038/s41586-024-07239-w
Abstrakt: Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA 1-3 . Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells 4-7 . 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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