Strand-specific single-cell 5hmC enables initial lineage bifurcation of individual cells into two subtrees
(A) Schematic shows a zygote with chromosomes containing high 5hmC levels (solid lines) undergoing three cell divisions. The newly synthesized strands contain very low levels of 5hmC (dotted lines). SCE events occur randomly during each cell cycle. Single cells are sequenced by using scAba-seq to quantify strand-specific 5hmC.
(B) Data showing mosaic pattern of strand-specific 5hmC in single cells obtained from an 8-cell mouse embryo. 5hmC counts within 2-Mb bins on the plus and minus strands are shown in orange and blue, respectively.
(C) OSS analysis on chromosome 7 places cell 8 in one 4-cell subtree and cells 1 and 2 in the other subtree. Performing OSS on all chromosomes places cells in one of these two 4-cell subtrees and reduces the complexity of the lineage reconstruction problem.