Resolving Cell Fate Decisions During Somatic Cell Reprogramming by Single-Cell RNA-Seq
72 Pages Posted: 13 Apr 2018 Sneak Peek Status: Review CompleteMore...
Cell makes fate decision with intrinsic and extrinsic cues. It has been difficult to define the precise decision process due to cellular heterogeneity. Here we map the cell fate continuum generated during somatic reprogramming by Oct4, Sox2 and Klf4 at single cell resolution. We show that the reprogramming cells initially march through mesenchyme-epithelial transition, then bifurcate into non-reprogramming (NR) and reprogramming (R) fates. The R cells continue to acquire Oct4 activation and then bifurcate again into Dppa5a chimera competent and Dppa5a- chimera incompetent cells. Mechanistically, we show that the NR/R bifurcation is controlled by Klf4 and Sox2 and the final Dppa5a rate-limiting step in part by IFN-γ, a cytokine activated during reprogramming. Our study identifies two previously unknown cell fate checkpoints along the reprogramming pathway, highlighting single-cell analysis as a tool to understand cell fate decisions.
Keywords: reprogramming; induced pluripotent stem cells; single-cell RNA sequencing (RNA-seq); bifurcation; cell fate decision
Suggested Citation: Suggested Citation