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. 2022 Jul 11;41(17):e108780. doi: 10.15252/embj.2021108780

Figure 5. Dynamic changes of metaregulons shape biologically distinct stages of neural crest and Schwann cell precursor development and differentiation.

Figure 5

  • A
    Subset of the tree containing the trajectory of trunk neural crest to immature Schwann cells.
  • B
    Progression of the metaregulons over the trajectory selected in (A), combined with developmental time. A metaregulon is the mean expression of all regulons composing a cluster over pseudotime.
  • C
    Trajectory coloured by metaregulons, with a selection of regulons composing them.
  • D
    Validation of SIX1 and Ets1 as markers for biasing towards sensory and glia fates, respectively. Scale bar is 50 μm in the overview picture and 10 μm in the insets. Stainings were repeated on two separate occasions on two embryos from the same litter. Cells surrounded by solid white lines correspond to SIX1-/Ets1+/SOX10+ SCPs or glial fate-biased progenitors, while cells surrounded by dashed yellow lines SIX1+/Ets1- or low/SOX10- or low sensory fate-biased progenitors.
  • E
    Normalised regulon activity scores of Ets1 and Six1 over the trajectory.
  • F
    Inter‐/intra‐correlation analysis of the target genes of Ets1 and Six1 regulons on nonintersecting windows of cells over the trajectory.
  • G, H
    Bifurcation analysis over two successive sensory branches, highlighting the early and late genes biasing towards “hub” cells (G) and satellite glia (H).
  • I
    Venn diagram of early genes expressed in the bifurcation between “hub” and satellite glia. Gene list shows the common genes between the two.

Data information: iSCs, immature Schwann cells; NCCs, neural crest cells.