Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 34 (8), 852-6

Single-cell 5hmC Sequencing Reveals Chromosome-Wide Cell-To-Cell Variability and Enables Lineage Reconstruction

Affiliations

Single-cell 5hmC Sequencing Reveals Chromosome-Wide Cell-To-Cell Variability and Enables Lineage Reconstruction

Dylan Mooijman et al. Nat Biotechnol.

Abstract

The epigenetic DNA modification 5-hydroxymethylcytosine (5hmC) has crucial roles in development and gene regulation. Quantifying the abundance of this epigenetic mark at the single-cell level could enable us to understand its roles. We present a single-cell, genome-wide and strand-specific 5hmC sequencing technology, based on 5hmC glucosylation and glucosylation-dependent digestion of DNA, that reveals pronounced cell-to-cell variability in the abundance of 5hmC on the two DNA strands of a given chromosome. We develop a mathematical model that reproduces the strand bias and use this model to make two predictions. First, the variation in strand bias should decrease when 5hmC turnover increases. Second, the strand bias of two sister cells should be strongly anti-correlated. We validate these predictions experimentally, and use our model to reconstruct lineages of two- and four-cell mouse embryos, showing that single-cell 5hmC sequencing can be used as a lineage reconstruction tool.

Similar articles

See all similar articles

Cited by 23 PubMed Central articles

See all "Cited by" articles

References

    1. Nature. 2013 Aug 8;500(7461):222-6 - PubMed
    1. Cell. 2008 Oct 17;135(2):216-26 - PubMed
    1. Cell Rep. 2012 Sep 27;2(3):666-73 - PubMed
    1. Cancer Res. 2007 Feb 1;67(3):946-50 - PubMed
    1. Science. 2014 Feb 14;343(6172):776-9 - PubMed

Publication types

LinkOut - more resources

Feedback