Shared regulation and functional relevance of local gene co-expression revealed by single cell analysis
Most human genes are co-expressed with a nearby gene. Previous studies have revealed this local gene co-expression to be widespread across chromosomes and across dozens of tissues. Yet, so far these studies used bulk RNA-seq, averaging gene expression measurements across millions of cells, thus bein...
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| Vydané v: | Communications biology Ročník 5; číslo 1; s. 876 - 11 |
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| Hlavní autori: | , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
London
Nature Publishing Group UK
26.08.2022
Nature Publishing Group Nature Portfolio |
| Predmet: | |
| ISSN: | 2399-3642, 2399-3642 |
| On-line prístup: | Získať plný text |
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| Shrnutí: | Most human genes are co-expressed with a nearby gene. Previous studies have revealed this local gene co-expression to be widespread across chromosomes and across dozens of tissues. Yet, so far these studies used bulk RNA-seq, averaging gene expression measurements across millions of cells, thus being unclear if this co-expression stems from transcription events in single cells. Here, we leverage single cell datasets in >85 individuals to identify gene co-expression across cells, unbiased by cell-type heterogeneity and benefiting from the co-occurrence of transcription events in single cells. We discover >3800 co-expressed gene pairs in two human cell types, induced pluripotent stem cells (iPSCs) and lymphoblastoid cell lines (LCLs) and (i) compare single cell to bulk RNA-seq in identifying local gene co-expression, (ii) show that many co-expressed genes – but not the majority – are composed of functionally related genes and (iii) using proteomics data, provide evidence that their co-expression is maintained up to the protein level. Finally, using single cell RNA-sequencing (scRNA-seq) and single cell ATAC-sequencing (scATAC-seq) data for the same single cells, we identify gene-enhancer associations and reveal that >95% of co-expressed gene pairs share regulatory elements. These results elucidate the potential reasons for co-expression in single cell gene regulatory networks and warrant a deeper study of shared regulatory elements, in view of explaining disease comorbidity due to affecting several genes. Our in-depth view of local gene co-expression and regulatory element co-activity advances our understanding of the shared regulatory architecture between genes.
Using single-cell data from cell lines, the co-expression of genes and co-activity of regulatory elements is analyzed, providing insight into shared architecture and regulation between genes. |
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| Bibliografia: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ISSN: | 2399-3642 2399-3642 |
| DOI: | 10.1038/s42003-022-03831-w |