Newborn and young adult (2 months) mouse dorsal skin cell culture time-series RNA-Seq

Organoid formation is critical to the progress of regenerative medicine. We use the formation of skin organoids from dissociated cells to study the self-organization process. Here we live-image the process which reveals an unexpectedly complex morphogenetic process: dissociated cells – aggregates – polarized cysts – fused cysts– planar skin – hair placodes. Transcriptome profiling and functional testing show orderly expression peaks of adhesion molecules, insulin-like growth factors, Wnts, extracellular matrix molecules, and matrix metalloproteinases are crucial to the sequential morphological transitions. We draw an analogy between these self-organizing morphogenetic behaviours and the self-assembly of molecules in biophysics, with different morphological stages connected by phase transition-like switches. Adult cells, normally stalled as aggregates, can be restored to reform hairy skin by reactivation of the self-organization process with timely supply of molecular cues. Physical processes and molecular events may work in tandem to achieve organoid self-formation in tissue engineering and in vivo. Overall design: Comparison of mRNA profiles in newborn and young adult (about 2 months) mouse dorsal skin reconstitution cells at different culture time points