(a) Lineage tree inferred by Monocle 21 using reverse graph embedding. See Online methods for details. Cell types identified based on marker genes are highlighted. (b) Same as (a) but clusters inferred by Monocle 2 are highlighted. (c) Shown are Monocle 2 derived lineage trees highlighting log2-transformed normalized transcript levels of Kit and Ly6a (multipotency), Dntt (lymphoid lineage), Ebf1 (B cell lineage), Siglech (plasmacytoid dendritic cells), Cd74 (conventional dendritic cells), Elane (neutrophils), Gata1 (erythrocyte lineage) and Thy1 (innate lymphoid cells). Monocle 2, which is an established method for the derivation of multi-branched lineage trees failed to resolve Thy1-postive innate lymphocyte progenitors from B cell progenitors and distributed pDC progenitors across several branches. Furthermore, the fixed assignment of a cell to a branch does not predict residual bias to one or more alternative lineages. A probabilistic view on the process of cell fate decision is more appropriate for capturing transitions between cell states biased towards distinct fates, and quantification of co-existing multi-lineage bias is not achieved by available algorithms for the prediction of lineage trees. Monocle 2 results are shown for 1,802 cells from three independent experiments with n = 4 mice.
1. Qiu, X. et al. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979–982 (2017).