Björn Reinius group

Research focus: X-chromosome inactivation

Our research is focused on revealing principal features of gene regulation, and in particular the regulation of active and inactive chromatin states. A main topic in the lab is X-chromosome inactivation.

Female cells contain two X chromosomes while male cells contain only one, and to balance the X-gene dose in female cells one X copy is kept transcriptionally silenced by the process of X-chromosome inactivation. This is achieved by remarkable remodeling of the inactive X chromosome, which drastically changes its chromatin structure, methylation patterns, and three-dimensional conformation – ultimately suppressing the expression of most of its genes.

By characterizing the epigenetic framework of X-chromosome inactivation, we reveal important properties of gene regulation. During the last years Reinius and colleagues pioneered the use of single-cell RNA-seq in the study of X-inactivation (Science 2014, Cell 2016, Nature Genetics 2016 among other publications).

Currently the Reinius lab is working to determine the X-inactive landscape across a wide range of in vivo tissues and cell types. This is accomplished by a comprehensive synthesis of newly developed concepts and techniques, including single-cell RNA-sequencing, chromatin accessibility and modification assays, mouse genetics and transgenics, and recently advanced computational methods for the analysis of allele-specific gene expression.

Knowledge gained form this research is of broad biological significance, and may reveal gene-regulatory features underlying variable expressivity and incomplete penetrance of X-linked traits and genetic disorders.

Advancing RNA/DNA sequencing technology: High-throughput sequencing is key in our work, and is increasingly utilized in Medicine. We are working to invent and improve methods for RNA and DNA sequencing – tailoring the protocols to maximize the information yield in the context of specific experiments.

Selected publications

* Co-first author, # Corresponding author

X-chromosome upregulation is driven by increased burst frequency.
Larsson AJM, Coucoravas C, Sandberg R, Reinius B#
Nat. Struct. Mol. Biol. 2019 Oct;26(10):963-969

Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq.
Reinius B*, Mold JE*, Ramsköld D, Deng Q, Johnsson P, Michaëlsson J, Frisén J, Sandberg R#.
Nat Genet. 2016 Nov;48(11):1430-1435. doi: 10.1038/ng.3678. Epub 2016 Sep 26.

Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos.
Petropoulos S*, Edsgärd D*, Reinius B*, Deng Q, Panula SP, Codeluppi S, Plaza Reyes A, Linnarsson S, Sandberg R#, Lanner F#.
Cell. 2016 May 5;165(4):1012-26. doi: 10.1016/j.cell.2016.03.023. Epub 2016 Apr 7.

Random monoallelic expression of autosomal genes: stochastic transcription and allele-level regulation.
Reinius B, Sandberg R#.
Nat Rev Genet. 2015 Nov;16(11):653-64. doi: 10.1038/nrg3888. Epub 2015 Oct 7. Review.

Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells.
Deng Q*, Ramsköld D*, Reinius B, Sandberg R#.
Science. 2014 Jan 10;343(6167):193-6. doi: 10.1126/science.1245316.

Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse.
Reinius B#, Shi C, Hengshuo L, Sandhu KS, Radomska KJ, Rosen GD, Lu L, Kullander K, Williams RW, Jazin E.
BMC Genomics. 2010 Nov 3;11:614. doi: 10.1186/1471-2164-11-614.

Group members